{"entity": "researcher", "timestamp": "2026-08-20T20:37:34.700Z", "family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "affiliations": ["Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.", "Science for Life Laboratory, Stockholm University, Solna, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f"}}, "publications": [{"entity": "publication", "iuid": "cddad9583da743ca99f4f837e46f08d5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cddad9583da743ca99f4f837e46f08d5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cddad9583da743ca99f4f837e46f08d5"}}, "title": "Cotranslational folding and maturation of HIV-1 protease.", "authors": [{"family": "Westerfield", "given": "Justin", "initials": "J", "orcid": "0000-0002-3937-5833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abd6b68fba914d529ef0ad62466a4ebc.json"}}, {"family": "Nicolaus", "given": "Felix", "initials": "F", "orcid": "0000-0001-9230-8544", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f47078a41e242c98a1b2a3c2ad0ebe9.json"}}, {"family": "Swanstrom", "given": "Ronald", "initials": "R", "orcid": "0000-0001-7777-0773", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a267fa86094b4ddb9a965c9663ad1b60.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2025-08-27", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "HIV-1 particle assembly depends critically on multiple proteolytic cleavages of viral polyproteins by the viral protease, PR. PR is translated as part of the Gag-Pro-Pol polyprotein, which undergoes autoproteolysis to liberate active, dimeric PR during virus particle maturation. Gag-Pro-Pol is produced via an infrequent -1 frameshifting event in ribosomes translating full length genomic RNA as Gag mRNA. Here, we study the cotranslational folding and autoproteolytic processing of frameshifted transframe-protease-reverse transcriptase (TF-PR-RT) constructs by in vitro translation. We demonstrate partial cotranslational folding of ribosome-bound PR at its conserved \u03b1-helix near the C terminus. Unexpectedly, we find that the initial dimerization of TF-PR-RT involves ribosome-bound nascent chains that are then not further cleaved. Moreover, only ribosome-bound nascent chains are substrates for PR-catalyzed processing. These observations are consistent with a model for virion assembly in which dimerization of a subset of Pro-Pol precursors leads to cleavage of PR monomers that then carry out the bulk of the proteolytic processing needed for virion maturation and infectivity.", "doi": "10.1101/2025.08.27.672612", "pmid": "40909734", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12407942"}, {"db": "pii", "key": "2025.08.27.672612"}], "notes": [], "created": "2026-08-20T11:07:04.077Z", "modified": "2026-08-20T11:07:04.152Z"}, {"entity": "publication", "iuid": "36b68ca5b04e4d5ca613883e68f05b76", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/36b68ca5b04e4d5ca613883e68f05b76.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/36b68ca5b04e4d5ca613883e68f05b76"}}, "title": "Cotranslational membrane insertion of the voltage-sensitive K+ channel KvAP.", "authors": [{"family": "Westerfield", "given": "Justin M", "initials": "JM"}, {"family": "Kozojedov\u00e1", "given": "Petra", "initials": "P", "orcid": "0009-0005-0015-6050", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/12843a92cb9344d1b5a19a0d6e6f96aa.json"}}, {"family": "Juli", "given": "Cara", "initials": "C"}, {"family": "Metola", "given": "Ane", "initials": "A", "orcid": "0000-0002-2885-7634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d15b6e5328914e6d8de881bd6a78a1a7.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2025-04-08", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "122", "issue": "14", "pages": "e2412492122", "issn-l": "0027-8424"}, "abstract": "Voltage-sensor domains (VSDs), found in many voltage-sensitive ion channels and enzymes, are composed of four transmembrane helices (TMHs), including the atypical, highly positively charged S4 helix. VSDs are cotranslationally inserted into the membrane, raising the question of how the highly charged S4 helix is integrated into the lipid bilayer as it exits the ribosome. Here, we have used force profile analysis (FPA) to follow the cotranslational insertion of the six-TMH KvAP voltage-sensitive ion channel into the Escherichia coli inner membrane. We find that the insertion process proceeds through three semi-independent steps: i) insertion of the S1-S2 helix hairpin, ii) insertion of the S3-S5 helices, and iii) insertion of the Pore and S6 helices. Our analysis highlights the importance of the concerted insertion of helical hairpins, the dramatic influence of the positively charged residues in S4, and the unexpectedly strong forces and effects on downstream TMHs elicited by amphipathic and re-entrant helices.", "doi": "10.1073/pnas.2412492122", "pmid": "40163725", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12002286"}], "notes": [], "created": "2026-08-20T09:31:34.716Z", "modified": "2026-08-20T09:31:34.872Z"}, {"entity": "publication", "iuid": "7afa31d399a742e7bb37e0ee13517180", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7afa31d399a742e7bb37e0ee13517180.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7afa31d399a742e7bb37e0ee13517180"}}, "title": "Sequence-dependent scale for translocon-mediated insertion of interfacial helices in membranes.", "authors": [{"family": "Grau", "given": "Brayan", "initials": "B", "orcid": "0000-0002-8582-023X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84bbceb1ffce4fa1b44ab539d4f86bf5.json"}}, {"family": "Kormos", "given": "Rian", "initials": "R", "orcid": "0000-0002-5831-1464", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3bff9dc82ac54755a607c671b297240e.json"}}, {"family": "Ba\u00f1\u00f3-Polo", "given": "Manuel", "initials": "M", "orcid": "0000-0002-4840-4480", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/437b412ddb624eeaa5bf74833b68c58d.json"}}, {"family": "Chen", "given": "Kehan", "initials": "K", "orcid": "0000-0003-0419-8360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e69b1eec821462f97b885305b2f9eb6.json"}}, {"family": "Garc\u00eda-Murria", "given": "Mar\u00eda J", "initials": "MJ"}, {"family": "Hajredini", "given": "Fatlum", "initials": "F", "orcid": "0000-0003-0656-6059", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b0adb58f6ac43b8947f560e5a2fd156.json"}}, {"family": "S\u00e1nchez Del Pino", "given": "Manuel M", "initials": "MM", "orcid": "0000-0001-9696-7600", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f44e2bb8541e4595aa1f6efb42fd0e6b.json"}}, {"family": "Jo", "given": "Hyunil", "initials": "H", "orcid": "0000-0002-4863-0779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e3bef1759a73460d934973c816ef7719.json"}}, {"family": "Mart\u00ednez-Gil", "given": "Luis", "initials": "L", "orcid": "0000-0002-9076-7760", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56836e0367c7450cacfbb5e78acd3783.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "DeGrado", "given": "William F", "initials": "WF", "orcid": "0000-0003-4745-263X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87ff63ab9e48487696328cf7f0d5c0f2.json"}}, {"family": "Mingarro", "given": "Ismael", "initials": "I", "orcid": "0000-0002-1910-1229", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a6c7a13940044c7bb968a17b920db2e.json"}}], "type": "journal article", "published": "2025-02-21", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "8", "pages": "eads6804", "issn-l": "2375-2548"}, "abstract": "Biological membranes consist of a lipid bilayer studded with integral and peripheral membrane proteins. Most \u03b1-helical membrane proteins require protein-conducting insertases known as translocons to assist in their membrane insertion and folding. While the sequence-dependent propensities for a helix to either translocate through the translocon or insert into the membrane have been codified into numerical hydrophobicity scales, the corresponding propensity to partition into the membrane interface remains unrevealed. By engineering diagnostic glycosylation sites around test peptide sequences inserted into a host protein, we devised a system that can differentiate between water-soluble, surface-bound, and transmembrane (TM) states of the sequence based on its glycosylation pattern. Using this system, we determined the sequence-dependent propensities for transfer from the translocon to a TM, interfacial, or extramembrane space and compared these propensities with the corresponding probability distributions determined from the sequences and structures of experimentally determined proteins.", "doi": "10.1126/sciadv.ads6804", "pmid": "39970206", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11837994"}], "notes": [], "created": "2026-08-20T11:59:02.273Z", "modified": "2026-08-20T11:59:02.695Z"}, {"entity": "publication", "iuid": "a31f9689bd3b42db8093b0be00b5a2ab", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a31f9689bd3b42db8093b0be00b5a2ab.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a31f9689bd3b42db8093b0be00b5a2ab"}}, "title": "Spc2 modulates substrate- and cleavage site-selection in the yeast signal peptidase complex.", "authors": [{"family": "Chung", "given": "Yeonji", "initials": "Y", "orcid": "0009-0000-9326-6008", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9664b267a5364f399a6f05be47bda85a.json"}}, {"family": "Yim", "given": "Chewon", "initials": "C", "orcid": "0000-0002-0200-8458", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e61668a1319a4d9eaf0f10d7823d42ba.json"}}, {"family": "Pereira", "given": "Gilberto P", "initials": "GP", "orcid": "0000-0002-6277-0006", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d70da5b204ee458dbb41c6b58bbe928f.json"}}, {"family": "Son", "given": "Sungjoon", "initials": "S", "orcid": "0009-0008-7613-2305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08db25ca40a94ed99490435f908b4078.json"}}, {"family": "Kj\u00f8lbye", "given": "Lisbeth R", "initials": "LR", "orcid": "0000-0003-2834-3411", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a1ce30e22b04e3ba42222b9cff63116.json"}}, {"family": "Mazurkiewicz", "given": "Lauren E", "initials": "LE", "orcid": "0000-0002-8045-6803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3bbb9a31648c4b77b3a7e4195f987321.json"}}, {"family": "Weeks", "given": "Amy M", "initials": "AM", "orcid": "0000-0003-4700-8256", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdcdd9f864094e76beae3c3e75e82d0d.json"}}, {"family": "F\u00f6rster", "given": "Friedrich", "initials": "F", "orcid": "0000-0002-6044-2746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ccae3beba62145a7a16f8254920f92ac.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Souza", "given": "Paulo C T", "initials": "PCT", "orcid": "0000-0003-0660-1301", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c424f06c2304ac89afed85d40e0a706.json"}}, {"family": "Kim", "given": "Hyun", "initials": "H", "orcid": "0000-0003-2076-9020", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77c6e34f86444f51b0642eb2967ee200.json"}}], "type": "journal article", "published": "2024-12-02", "journal": {"title": "J. Cell Biol.", "issn": "1540-8140", "volume": "223", "issue": "12", "issn-l": "0021-9525"}, "abstract": "Secretory proteins are critically dependent on the correct processing of their signal sequence by the signal peptidase complex (SPC). This step, which is essential for the proper folding and localization of proteins in eukaryotic cells, is still not fully understood. In eukaryotes, the SPC comprises four evolutionarily conserved membrane subunits (Spc1-3 and Sec11). Here, we investigated the role of Spc2, examining SPC cleavage efficiency on various models and natural signal sequences in yeast cells depleted of or with mutations in Spc2. Our data show that discrimination between substrates and identification of the cleavage site by SPC is compromised when Spc2 is absent or mutated. Molecular dynamics simulation of the yeast SPC AlphaFold2-Multimer model indicates that membrane thinning at the center of SPC is reduced without Spc2, suggesting a molecular explanation for the altered substrate recognition properties of SPC lacking Spc2. These results provide new insights into the molecular mechanisms by which SPC governs protein biogenesis.", "doi": "10.1083/jcb.202211035", "pmid": "39565596", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11579918"}, {"db": "pii", "key": "277099"}], "notes": [], "created": "2026-08-20T09:38:02.527Z", "modified": "2026-08-20T09:38:03.016Z"}, {"entity": "publication", "iuid": "cb53edd6210042f8b2d38fc24ce7b3be", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cb53edd6210042f8b2d38fc24ce7b3be.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cb53edd6210042f8b2d38fc24ce7b3be"}}, "title": "Sequence-dependent scale for translocon-mediated insertion of interfacial helices in membranes", "authors": [{"family": "Grau", "given": "Brayan", "initials": "B", "orcid": "0000-0002-8582-023X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84bbceb1ffce4fa1b44ab539d4f86bf5.json"}}, {"family": "Kormos", "given": "Rian", "initials": "R"}, {"family": "Ba\u00f1\u00f3-Polo", "given": "Manuel", "initials": "M"}, {"family": "Chen", "given": "Kehan", "initials": "K"}, {"family": "Garc\u00eda-Murria", "given": "Mar\u00eda J", "initials": "MJ"}, {"family": "Hajredini", "given": "Fatlum", "initials": "F"}, {"family": "S\u00e1nchez del Pino", "given": "Manuel M", "initials": "MM"}, {"family": "Jo", "given": "Hyunil", "initials": "H"}, {"family": "Mart\u00ednez-Gil", "given": "Luis", "initials": "L"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "DeGrado", "given": "William F", "initials": "WF", "orcid": "0000-0003-4745-263X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87ff63ab9e48487696328cf7f0d5c0f2.json"}}, {"family": "Mingarro", "given": "Ismael", "initials": "I", "orcid": "0000-0002-1910-1229", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a6c7a13940044c7bb968a17b920db2e.json"}}], "type": "posted-content", "published": "2024-10-25", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2024.10.23.619793", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:58:56.137Z", "modified": "2026-08-20T10:58:56.276Z"}, {"entity": "publication", "iuid": "af3012effc7e4c12972453056d7e8de4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/af3012effc7e4c12972453056d7e8de4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/af3012effc7e4c12972453056d7e8de4"}}, "title": "Single-residue effects on the behavior of a nascent polypeptide chain inside the ribosome exit tunnel.", "authors": [{"family": "Pardo-Avila", "given": "F\u00e1tima", "initials": "F", "orcid": "0009-0002-9040-4684", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/edb6b877440e40f0a4f0272a7ac4f5a7.json"}}, {"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}, {"family": "Levitt", "given": "Michael", "initials": "M", "orcid": "0000-0002-8414-7397", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea8efb5af79543d4ab9a357b889abe37.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2024-08-20", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Nascent polypeptide chains (NCs) are extruded from the ribosome through an exit tunnel (ET) traversing the large ribosomal subunit. The ET's irregular and chemically complex wall allows for various NC-ET interactions. Translational arrest peptides (APs) bind in the ET to induce translational arrest, a property that can be exploited to study NC-ET interactions by Force Profile Analysis (FPA). We employed FPA and molecular dynamics (MD) simulations to investigate how individual residues placed in a glycine-serine repeat segment within an AP-stalled NC interact with the ET to exert a pulling force on the AP and release stalling. Our results indicate that large and hydrophobic residues generate a pulling force on the NC when placed \u227310 residues away from the peptidyl transfer center (PTC). Moreover, an asparagine placed 12 residues from the PTC makes a specific stabilizing interaction with the tip of ribosomal protein uL22 that reduces the pulling force on the NC, while a lysine or leucine residue in the same position increases the pulling force. Finally, the MD simulations suggest how the Mannheimia succiniproducens SecM AP interacts with the ET to promote translational stalling.", "doi": "10.1101/2024.08.20.608737", "pmid": "39229094", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11370347"}, {"db": "pii", "key": "2024.08.20.608737"}], "notes": [], "created": "2026-08-20T10:56:12.120Z", "modified": "2026-08-20T10:56:12.255Z"}, {"entity": "publication", "iuid": "7cc03b338f0e4d23873d077a78419126", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7cc03b338f0e4d23873d077a78419126.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7cc03b338f0e4d23873d077a78419126"}}, "title": "Cotranslational membrane insertion of the voltage-sensitive K + channel KvAP", "authors": [{"family": "Westerfield", "given": "Justin M", "initials": "JM", "orcid": "0000-0002-3937-5833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abd6b68fba914d529ef0ad62466a4ebc.json"}}, {"family": "Kozojedov\u00e1", "given": "Petra", "initials": "P"}, {"family": "Juli", "given": "Cara", "initials": "C"}, {"family": "Metola", "given": "Ane", "initials": "A", "orcid": "0000-0002-2885-7634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d15b6e5328914e6d8de881bd6a78a1a7.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2024-05-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2024.05.28.596144", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:54:57.840Z", "modified": "2026-08-20T10:54:57.924Z"}, {"entity": "publication", "iuid": "d785496149464411afb7ac5515a368d5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d785496149464411afb7ac5515a368d5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d785496149464411afb7ac5515a368d5"}}, "title": "Cotranslational folding of human growth hormone in vitro and in Escherichia coli.", "authors": [{"family": "Mermans", "given": "Daphne", "initials": "D"}, {"family": "Nicolaus", "given": "Felix", "initials": "F"}, {"family": "Baygin", "given": "Aysel", "initials": "A"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "letter", "published": "2023-05-00", "journal": {"title": "FEBS Lett.", "issn": "1873-3468", "volume": "597", "issue": "10", "pages": "1355-1362", "issn-l": "0014-5793"}, "abstract": "Human growth hormone (hGH) is a four-helix bundle protein of considerable pharmacological interest. Recombinant hGH is produced in bacteria, yet little is known about its folding during expression in Escherichia coli. We have studied the cotranslational folding of hGH using force profile analysis (FPA), both during in vitro translation in the absence and presence of the chaperone trigger factor (TF), and when expressed in E. coli. We find that the main folding transition starts before hGH is completely released from the ribosome, and that it can interact with TF and possibly other chaperones.", "doi": "10.1002/1873-3468.14562", "pmid": "36520514", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T06:25:25.524Z", "modified": "2026-08-20T06:25:25.580Z"}, {"entity": "publication", "iuid": "6bf8d0af57d843259791c3aac6a8439f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6bf8d0af57d843259791c3aac6a8439f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6bf8d0af57d843259791c3aac6a8439f"}}, "title": "Cotranslational folding and assembly of the dimeric Escherichia coli inner membrane protein EmrE.", "authors": [{"family": "Mermans", "given": "Daphne", "initials": "D", "orcid": "0000-0001-6001-5608", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27a2db6738b94dd188eff74e4705bf37.json"}}, {"family": "Nicolaus", "given": "Felix", "initials": "F", "orcid": "0000-0001-9230-8544", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f47078a41e242c98a1b2a3c2ad0ebe9.json"}}, {"family": "Fleisch", "given": "Klara", "initials": "K"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2022-08-30", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "119", "issue": "35", "pages": "e2205810119", "issn-l": "0027-8424"}, "abstract": "In recent years, it has become clear that many homo- and heterodimeric cytoplasmic proteins in both prokaryotic and eukaryotic cells start to dimerize cotranslationally (i.e., while at least one of the two chains is still attached to the ribosome). Whether this is also possible for integral membrane proteins is, however, unknown. Here, we apply force profile analysis (FPA)-a method where a translational arrest peptide (AP) engineered into the polypeptide chain is used to detect force generated on the nascent chain during membrane insertion-to demonstrate cotranslational interactions between a fully membrane-inserted monomer and a nascent, ribosome-tethered monomer of the Escherichia coli inner membrane protein EmrE. Similar cotranslational interactions are also seen when the two monomers are fused into a single polypeptide. Further, we uncover an apparent intrachain interaction between E14 in transmembrane helix 1 (TMH1) and S64 in TMH3 that forms at a precise nascent chain length during cotranslational membrane insertion of an EmrE monomer. Like soluble proteins, inner membrane proteins thus appear to be able to both start to fold and start to dimerize during the cotranslational membrane insertion process.", "doi": "10.1073/pnas.2205810119", "pmid": "35994672", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9436324"}], "notes": [], "created": "2026-08-20T09:31:11.724Z", "modified": "2026-08-20T09:31:11.884Z"}, {"entity": "publication", "iuid": "1766662431e64f609cf65da4fe74747d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1766662431e64f609cf65da4fe74747d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1766662431e64f609cf65da4fe74747d"}}, "title": "Cotranslational folding of human growth hormone in vitro and in Escherichia coli", "authors": [{"family": "Mermans", "given": "Daphne", "initials": "D"}, {"family": "Nicolaus", "given": "Felix", "initials": "F"}, {"family": "Baygin", "given": "Aysel", "initials": "A"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2022-08-08", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2022.08.08.503169", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:12:52.851Z", "modified": "2026-08-20T10:12:52.896Z"}, {"entity": "publication", "iuid": "ee8276c230e948eca507f426d4f50e57", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ee8276c230e948eca507f426d4f50e57.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ee8276c230e948eca507f426d4f50e57"}}, "title": "Cotranslational folding and assembly of the dimeric E. coli inner membrane protein EmrE", "authors": [{"family": "Mermans", "given": "Daphne", "initials": "D"}, {"family": "Nicolaus", "given": "Felix", "initials": "F"}, {"family": "Fleisch", "given": "Klara", "initials": "K"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2022-04-02", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2022.04.02.486806", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:10:46.541Z", "modified": "2026-08-20T10:10:46.555Z"}, {"entity": "publication", "iuid": "64c679e13f6c41dbb14953b092b0892e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/64c679e13f6c41dbb14953b092b0892e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/64c679e13f6c41dbb14953b092b0892e"}}, "title": "Upstream charged and hydrophobic residues impact the timing of membrane insertion of transmembrane helices.", "authors": [{"family": "Nicolaus", "given": "Felix", "initials": "F"}, {"family": "Ibrahimi", "given": "Fatima", "initials": "F"}, {"family": "den Besten", "given": "Anne", "initials": "A"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2022-04-00", "journal": {"title": "FEBS Lett.", "issn": "1873-3468", "volume": "596", "issue": "8", "pages": "1004-1012", "issn-l": "0014-5793"}, "abstract": "During SecYEG-mediated cotranslational insertion of membrane proteins, transmembrane helices (TMHs) first make contact with the membrane when their N-terminal end is ~ 45 residues away from the peptidyl transferase centre. However, we recently uncovered instances where the first contact is delayed by up to ~ 10 residues. Here, we recapitulate these effects using a model TMH fused to two short segments from the Escherichia coli inner membrane protein BtuC: a positively charged loop and a re-entrant loop. We show that the critical residues are two Arg residues in the positively charged loop and four hydrophobic residues in the re-entrant loop. Thus, both electrostatic and hydrophobic interactions involving sequence elements that are not part of a TMH can impact the way the latter behaves during membrane insertion.", "doi": "10.1002/1873-3468.14286", "pmid": "35038773", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T06:25:23.608Z", "modified": "2026-08-20T06:25:23.666Z"}, {"entity": "publication", "iuid": "62cce2b4009d4079aacf4cffeb50fdd8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/62cce2b4009d4079aacf4cffeb50fdd8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/62cce2b4009d4079aacf4cffeb50fdd8"}}, "title": "Upstream charged and hydrophobic residues impact the timing of membrane insertion of transmembrane helices", "authors": [{"family": "Nicolaus", "given": "Felix", "initials": "F"}, {"family": "Ibrahimi", "given": "Fatima", "initials": "F"}, {"family": "den Besten", "given": "Anne", "initials": "A"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2021-12-24", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2021.12.23.474019", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:07:57.903Z", "modified": "2026-08-20T10:07:57.955Z"}, {"entity": "publication", "iuid": "d3c8b97f7d4647dc9088d1705ac540e7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d3c8b97f7d4647dc9088d1705ac540e7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d3c8b97f7d4647dc9088d1705ac540e7"}}, "title": "SignalP 6.0 achieves signal peptide prediction across all types using protein language models", "authors": [{"family": "Teufel", "given": "Felix", "initials": "F", "orcid": "0000-0003-1275-8065", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d5809964f694f7fb16e0745dbb645d5.json"}}, {"family": "Armenteros", "given": "Jos\u00e9 Juan Almagro", "initials": "JJA"}, {"family": "Johansen", "given": "Alexander Rosenberg", "initials": "AR"}, {"family": "G\u00edslason", "given": "Magn\u00fas Halld\u00f3r", "initials": "MH"}, {"family": "Pihl", "given": "Silas Irby", "initials": "SI"}, {"family": "Tsirigos", "given": "Konstantinos D", "initials": "KD", "orcid": "0000-0001-5280-1107", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85e1896a52d04cb7b4475ebba4d17505.json"}}, {"family": "Winther", "given": "Ole", "initials": "O", "orcid": "0000-0002-1966-3205", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9dea7f2a81d249cd99f8dec60f422770.json"}}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Nielsen", "given": "Henrik", "initials": "H", "orcid": "0000-0002-9412-9643", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95aab73521844700a8137cfc2cb287b0.json"}}], "type": "posted-content", "published": "2021-06-10", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2021.06.09.447770", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:04:45.794Z", "modified": "2026-08-20T10:04:45.920Z"}, {"entity": "publication", "iuid": "10051fb20f9a490c8d7fafa4d0b1886a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/10051fb20f9a490c8d7fafa4d0b1886a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/10051fb20f9a490c8d7fafa4d0b1886a"}}, "title": "Residue-by-residue analysis of cotranslational membrane protein integration in vivo.", "authors": [{"family": "Nicolaus", "given": "Felix", "initials": "F", "orcid": "0000-0001-9230-8544", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f47078a41e242c98a1b2a3c2ad0ebe9.json"}}, {"family": "Metola", "given": "Ane", "initials": "A", "orcid": "0000-0002-2885-7634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d15b6e5328914e6d8de881bd6a78a1a7.json"}}, {"family": "Mermans", "given": "Daphne", "initials": "D", "orcid": "0000-0001-6001-5608", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27a2db6738b94dd188eff74e4705bf37.json"}}, {"family": "Liljenstr\u00f6m", "given": "Amanda", "initials": "A"}, {"family": "Kr\u010d", "given": "Ajda", "initials": "A"}, {"family": "Abdullahi", "given": "Salmo Mohammed", "initials": "SM"}, {"family": "Zimmer", "given": "Matthew", "initials": "M", "orcid": "0000-0002-1437-2636", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab4c6e06a9a84cf9b710748f1ad659bf.json"}}, {"family": "Miller Iii", "given": "Thomas F", "initials": "TF", "orcid": "0000-0002-1882-5380", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27d29bc3f81346afa7ca8b713df24a86.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2021-02-08", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "10", "issn-l": "2050-084X"}, "abstract": "We follow the cotranslational biosynthesis of three multispanning Escherichia coli inner membrane proteins in vivo using high-resolution force profile analysis. The force profiles show that the nascent chain is subjected to rapidly varying pulling forces during translation and reveal unexpected complexities in the membrane integration process. We find that an N-terminal cytoplasmic domain can fold in the ribosome exit tunnel before membrane integration starts, that charged residues and membrane-interacting segments such as re-entrant loops and surface helices flanking a transmembrane helix (TMH) can advance or delay membrane integration, and that point mutations in an upstream TMH can affect the pulling forces generated by downstream TMHs in a highly position-dependent manner, suggestive of residue-specific interactions between TMHs during the integration process. Our results support the 'sliding' model of translocon-mediated membrane protein integration, in which hydrophobic segments are continually exposed to the lipid bilayer during their passage through the SecYEG translocon.", "doi": "10.7554/eLife.64302", "pmid": "33554862", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7886326"}, {"db": "pii", "key": "64302"}], "notes": [], "created": "2026-08-20T13:53:20.604Z", "modified": "2026-08-20T13:53:20.732Z"}, {"entity": "publication", "iuid": "f045bb18c2a748879939f71c6872f94c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f045bb18c2a748879939f71c6872f94c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f045bb18c2a748879939f71c6872f94c"}}, "title": "Cotranslational folding of a periplasmic protein domain in Escherichia coli", "authors": [{"family": "Sandhu", "given": "Hena", "initials": "H"}, {"family": "Hedman", "given": "Rickard", "initials": "R"}, {"family": "Cymer", "given": "Florian", "initials": "F"}, {"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}, {"family": "Ismail", "given": "Nurzian", "initials": "N"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2021-02-06", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2021.02.06.430026", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:02:33.167Z", "modified": "2026-08-20T10:02:33.225Z"}, {"entity": "publication", "iuid": "df2c8bb10e134c1bbdb453843cfa9793", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/df2c8bb10e134c1bbdb453843cfa9793.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/df2c8bb10e134c1bbdb453843cfa9793"}}, "title": "Author response: Residue-by-residue analysis of cotranslational membrane protein integration in vivo", "authors": [{"family": "Nicolaus", "given": "Felix", "initials": "F", "orcid": "0000-0001-9230-8544", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f47078a41e242c98a1b2a3c2ad0ebe9.json"}}, {"family": "Metola", "given": "Ane", "initials": "A", "orcid": "0000-0002-2885-7634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d15b6e5328914e6d8de881bd6a78a1a7.json"}}, {"family": "Mermans", "given": "Daphne", "initials": "D", "orcid": "0000-0001-6001-5608", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27a2db6738b94dd188eff74e4705bf37.json"}}, {"family": "Liljenstr\u00f6m", "given": "Amanda", "initials": "A"}, {"family": "Kr\u010d", "given": "Ajda", "initials": "A"}, {"family": "Abdullahi", "given": "Salmo Mohammed", "initials": "SM"}, {"family": "Zimmer", "given": "Matthew", "initials": "M", "orcid": "0000-0002-1437-2636", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab4c6e06a9a84cf9b710748f1ad659bf.json"}}, {"family": "Miller III", "given": "Thomas F", "initials": "TF", "orcid": "0000-0002-1882-5380", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27d29bc3f81346afa7ca8b713df24a86.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "peer-review", "published": "2021-02-01", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.64302.sa2", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:53:22.637Z", "modified": "2026-08-20T13:53:22.681Z"}, {"entity": "publication", "iuid": "71f0280c5fa44aff85961bc6c771cbd5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/71f0280c5fa44aff85961bc6c771cbd5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/71f0280c5fa44aff85961bc6c771cbd5"}}, "title": "Cotranslational folding of alkaline phosphatase in the periplasm of Escherichia coli.", "authors": [{"family": "Elfageih", "given": "Rageia", "initials": "R", "orcid": "0000-0003-0506-1470", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a76db32fb3f44bd992423d22ebef0293.json"}}, {"family": "Karyolaimos", "given": "Alexandros", "initials": "A", "orcid": "0000-0003-2264-3958", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d43d202f8684c09a3e34ca0d26cabc4.json"}}, {"family": "Kemp", "given": "Grant", "initials": "G", "orcid": "0000-0001-5125-2740", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d715b8af2972418aa144b2ca11487ce4.json"}}, {"family": "de Gier", "given": "Jan-Willem", "initials": "JW", "orcid": "0000-0001-5537-4358", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5868d65a24344c5da61ca3cacd29a558.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Protein Sci.", "issn": "1469-896X", "volume": "29", "issue": "10", "pages": "2028-2037", "issn-l": "0961-8368"}, "abstract": "Cotranslational protein folding studies using Force Profile Analysis, a method where the SecM translational arrest peptide is used to detect folding-induced forces acting on the nascent polypeptide, have so far been limited mainly to small domains of cytosolic proteins that fold in close proximity to the translating ribosome. In this study, we investigate the cotranslational folding of the periplasmic, disulfide bond-containing Escherichia coli protein alkaline phosphatase (PhoA) in a wild-type strain background and a strain background devoid of the periplasmic thiol: disulfide interchange protein DsbA. We find that folding-induced forces can be transmitted via the nascent chain from the periplasm to the polypeptide transferase center in the ribosome, a distance of ~160 \u00c5, and that PhoA appears to fold cotranslationally via at least two disulfide-stabilized folding intermediates. Thus, Force Profile Analysis can be used to study cotranslational folding of proteins in an extra-cytosolic compartment, like the periplasm.", "doi": "10.1002/pro.3927", "pmid": "32790204", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7513700"}], "notes": [], "created": "2026-08-20T06:35:05.418Z", "modified": "2026-08-20T06:35:05.625Z"}, {"entity": "publication", "iuid": "877eb77b11e14587a9a85fc11460be41", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/877eb77b11e14587a9a85fc11460be41.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/877eb77b11e14587a9a85fc11460be41"}}, "title": "Residue-by-residue analysis of cotranslational membrane protein integration in vivo", "authors": [{"family": "Nicolaus", "given": "Felix", "initials": "F"}, {"family": "Metola", "given": "Ane", "initials": "A"}, {"family": "Mermans", "given": "Daphne", "initials": "D"}, {"family": "Liljenstr\u00f6m", "given": "Amanda", "initials": "A"}, {"family": "Kr\u010d", "given": "Ajda", "initials": "A"}, {"family": "Abdullahi", "given": "Salmo Mohammed", "initials": "SM"}, {"family": "Zimmer", "given": "Matthew", "initials": "M"}, {"family": "Miller", "given": "Thomas F", "initials": "TF"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2020-09-28", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.09.27.315283", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:59:19.406Z", "modified": "2026-08-20T09:59:19.474Z"}, {"entity": "publication", "iuid": "4a7cb3934b1f44359966f38a422fae00", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4a7cb3934b1f44359966f38a422fae00.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4a7cb3934b1f44359966f38a422fae00"}}, "title": "Cotranslational folding of alkaline phosphatase in the periplasm of Escherichia coli", "authors": [{"family": "Elfageih", "given": "Rageia", "initials": "R"}, {"family": "Karyolaimos", "given": "Alexandros", "initials": "A", "orcid": "0000-0003-2264-3958", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d43d202f8684c09a3e34ca0d26cabc4.json"}}, {"family": "Kemp", "given": "Grant", "initials": "G", "orcid": "0000-0001-5125-2740", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d715b8af2972418aa144b2ca11487ce4.json"}}, {"family": "de Gier", "given": "Jan Willem", "initials": "JW", "orcid": "0000-0001-5537-4358", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5868d65a24344c5da61ca3cacd29a558.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}], "type": "posted-content", "published": "2020-07-06", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.07.06.189464", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:58:02.348Z", "modified": "2026-08-20T09:58:02.461Z"}, {"entity": "publication", "iuid": "811141c16e52452d9cf2acf9eab6ddba", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/811141c16e52452d9cf2acf9eab6ddba.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/811141c16e52452d9cf2acf9eab6ddba"}}, "title": "The ribosome modulates folding inside the ribosomal exit tunnel", "authors": [{"family": "Wruck", "given": "Florian", "initials": "F"}, {"family": "Tian", "given": "Pengfei", "initials": "P", "orcid": "0000-0003-0255-8692", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c8345e3930e4a52b396837a1c099e3f.json"}}, {"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}, {"family": "Best", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7893-3543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36c5cc15e14e412fb8798666bd48f00f.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Tans", "given": "Sander J", "initials": "SJ", "orcid": "0000-0002-7131-2568", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/89eebe8050034729afe2d4063e767582.json"}}, {"family": "Katranidis", "given": "Alexandros", "initials": "A", "orcid": "0000-0002-1785-1659", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4b148b128428419ba9b2e759ca159691.json"}}], "type": "posted-content", "published": "2020-07-01", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.06.30.180224", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:57:41.544Z", "modified": "2026-08-20T09:57:41.643Z"}, {"entity": "publication", "iuid": "529bcd0b6fc44702ac6b78b88503b316", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/529bcd0b6fc44702ac6b78b88503b316.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/529bcd0b6fc44702ac6b78b88503b316"}}, "title": "Cotranslational folding cooperativity of contiguous domains of \u03b1-spectrin.", "authors": [{"family": "Kemp", "given": "Grant", "initials": "G", "orcid": "0000-0001-5125-2740", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d715b8af2972418aa144b2ca11487ce4.json"}}, {"family": "Nilsson", "given": "Ola B", "initials": "OB"}, {"family": "Tian", "given": "Pengfei", "initials": "P", "orcid": "0000-0003-0255-8692", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c8345e3930e4a52b396837a1c099e3f.json"}}, {"family": "Best", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7893-3543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36c5cc15e14e412fb8798666bd48f00f.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2020-06-23", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "25", "pages": "14119-14126", "issn-l": "0027-8424"}, "abstract": "Proteins synthesized in the cell can begin to fold during translation before the entire polypeptide has been produced, which may be particularly relevant to the folding of multidomain proteins. Here, we study the cotranslational folding of adjacent domains from the cytoskeletal protein \u03b1-spectrin using force profile analysis (FPA). Specifically, we investigate how the cotranslational folding behavior of the R15 and R16 domains are affected by their neighboring R14 and R16, and R15 and R17 domains, respectively. Our results show that the domains impact each other's folding in distinct ways that may be important for the efficient assembly of \u03b1-spectrin, and may reduce its dependence on chaperones. Furthermore, we directly relate the experimentally observed yield of full-length protein in the FPA assay to the force exerted by the folding protein in piconewtons. By combining pulse-chase experiments to measure the rate at which the arrested protein is converted into full-length protein with a Bell model of force-induced rupture, we estimate that the R16 domain exerts a maximal force on the nascent chain of \u223c15 pN during cotranslational folding.", "doi": "10.1073/pnas.1909683117", "pmid": "32513720", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7322005"}, {"db": "pii", "key": "1909683117"}], "notes": [], "created": "2026-08-20T09:30:31.613Z", "modified": "2026-08-20T09:30:31.734Z"}, {"entity": "publication", "iuid": "1747f563e3d0432b8c0965b609614d6b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1747f563e3d0432b8c0965b609614d6b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1747f563e3d0432b8c0965b609614d6b"}}, "title": "Detecting sequence signals in targeting peptides using deep learning.", "authors": [{"family": "Almagro Armenteros", "given": "Jose Juan", "initials": "JJ"}, {"family": "Salvatore", "given": "Marco", "initials": "M", "orcid": "0000-0001-5775-0417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cc13d7ecab9d4dc6b5330f387678a699.json"}}, {"family": "Emanuelsson", "given": "Olof", "initials": "O", "orcid": "0000-0002-8879-9245", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a51c22f2bc594fe3a349bec5363f394f.json"}}, {"family": "Winther", "given": "Ole", "initials": "O"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Elofsson", "given": "Arne", "initials": "A", "orcid": "0000-0002-7115-9751", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/248e70e81bd64f31a5f83e6e329bba95.json"}}, {"family": "Nielsen", "given": "Henrik", "initials": "H", "orcid": "0000-0002-9412-9643", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95aab73521844700a8137cfc2cb287b0.json"}}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "volume": "2", "issue": "5", "issn-l": null}, "abstract": "In bioinformatics, machine learning methods have been used to predict features embedded in the sequences. In contrast to what is generally assumed, machine learning approaches can also provide new insights into the underlying biology. Here, we demonstrate this by presenting TargetP 2.0, a novel state-of-the-art method to identify N-terminal sorting signals, which direct proteins to the secretory pathway, mitochondria, and chloroplasts or other plastids. By examining the strongest signals from the attention layer in the network, we find that the second residue in the protein, that is, the one following the initial methionine, has a strong influence on the classification. We observe that two-thirds of chloroplast and thylakoid transit peptides have an alanine in position 2, compared with 20% in other plant proteins. We also note that in fungi and single-celled eukaryotes, less than 30% of the targeting peptides have an amino acid that allows the removal of the N-terminal methionine compared with 60% for the proteins without targeting peptide. The importance of this feature for predictions has not been highlighted before.", "doi": "10.26508/lsa.201900429", "pmid": "31570514", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6769257"}, {"db": "pii", "key": "2/5/e201900429"}], "notes": [], "created": "2026-08-20T13:03:51.409Z", "modified": "2026-08-20T13:03:51.559Z"}, {"entity": "publication", "iuid": "a98919675c764ca8bc9e4e8ab981ccb8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a98919675c764ca8bc9e4e8ab981ccb8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a98919675c764ca8bc9e4e8ab981ccb8"}}, "title": "Dynamic membrane topology in an unassembled membrane protein.", "authors": [{"family": "Seurig", "given": "Maximilian", "initials": "M", "orcid": "0000-0001-7962-5748", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b604f05c3b743f0ac768ecca6362ae9.json"}}, {"family": "Ek", "given": "Moira", "initials": "M"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Fluman", "given": "Nir", "initials": "N", "orcid": "0000-0001-9909-0779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4877a1d13c864bdf88de5bc383750994.json"}}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "15", "issue": "10", "pages": "945-948", "issn-l": "1552-4450"}, "abstract": "Helical membrane proteins are typically assumed to attain stable transmembrane topologies immediately upon co-translational membrane insertion. Here we show that unassembled monomers of the small multidrug resistance (SMR) family exist in a dynamic equilibrium where the N-terminal transmembrane helix flips in and out of the membrane, with rates that depend on dimerization and the polypeptide sequence. Thus, membrane topology can display rapid dynamics in vivo and can be regulated by post-translational assembly.", "doi": "10.1038/s41589-019-0356-9", "pmid": "31501590", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s41589-019-0356-9"}], "notes": [], "created": "2026-08-20T09:00:22.822Z", "modified": "2026-08-20T09:00:22.955Z"}, {"entity": "publication", "iuid": "c8fdfd804f98430294ec82fcf9f251df", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c8fdfd804f98430294ec82fcf9f251df.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c8fdfd804f98430294ec82fcf9f251df"}}, "title": "Structural and mutational analysis of the ribosome-arresting human XBP1u.", "authors": [{"family": "Shanmuganathan", "given": "Vivekanandan", "initials": "V"}, {"family": "Schiller", "given": "Nina", "initials": "N"}, {"family": "Magoulopoulou", "given": "Anastasia", "initials": "A"}, {"family": "Cheng", "given": "Jingdong", "initials": "J"}, {"family": "Braunger", "given": "Katharina", "initials": "K", "orcid": "0000-0002-9067-2155", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b39fb3443274977a68d01fa57862b6d.json"}}, {"family": "Cymer", "given": "Florian", "initials": "F"}, {"family": "Berninghausen", "given": "Otto", "initials": "O"}, {"family": "Beatrix", "given": "Birgitta", "initials": "B"}, {"family": "Kohno", "given": "Kenji", "initials": "K", "orcid": "0000-0002-3503-6551", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e2a1db1d762d47e48ad86f25b7ae5962.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Beckmann", "given": "Roland", "initials": "R", "orcid": "0000-0003-4291-3898", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/db3a9ba195ec4b5385f2c415ce1f4720.json"}}], "type": "journal article", "published": "2019-06-27", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "8", "issn-l": "2050-084X"}, "abstract": "XBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 \u00c5 cryo-EM structure of the stalled human XBP1u AP. It forms a unique turn in the ribosomal exit tunnel proximal to the peptidyl transferase center where it causes a subtle distortion, thereby explaining the temporary translational arrest induced by XBP1u. During ribosomal pausing the hydrophobic region 2 (HR2) of XBP1u is recognized by SRP, but fails to efficiently gate the Sec61 translocon. An exhaustive mutagenesis scan of the XBP1u AP revealed that only 8 out of 20 mutagenized positions are optimal; in the remaining 12 positions, we identify 55 different mutations increase the level of translational arrest. Thus, the wildtype XBP1u AP induces only an intermediate level of translational arrest, allowing efficient targeting by SRP without activating the Sec61 channel.", "doi": "10.7554/eLife.46267", "pmid": "31246176", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6624018"}, {"db": "pii", "key": "46267"}], "notes": [], "created": "2026-08-20T13:52:46.645Z", "modified": "2026-08-20T13:52:46.685Z"}, {"entity": "publication", "iuid": "0c727bba3fcb4a39be867a4a424af099", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0c727bba3fcb4a39be867a4a424af099.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0c727bba3fcb4a39be867a4a424af099"}}, "title": "Author response: Structural and mutational analysis of the ribosome-arresting human XBP1u", "authors": [{"family": "Shanmuganathan", "given": "Vivekanandan", "initials": "V"}, {"family": "Schiller", "given": "Nina", "initials": "N"}, {"family": "Magoulopoulou", "given": "Anastasia", "initials": "A"}, {"family": "Cheng", "given": "Jingdong", "initials": "J"}, {"family": "Braunger", "given": "Katharina", "initials": "K", "orcid": "0000-0002-9067-2155", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b39fb3443274977a68d01fa57862b6d.json"}}, {"family": "Cymer", "given": "Florian", "initials": "F"}, {"family": "Berninghausen", "given": "Otto", "initials": "O"}, {"family": "Beatrix", "given": "Birgitta", "initials": "B"}, {"family": "Kohno", "given": "Kenji", "initials": "K", "orcid": "0000-0002-3503-6551", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e2a1db1d762d47e48ad86f25b7ae5962.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Beckmann", "given": "Roland", "initials": "R", "orcid": "0000-0003-4291-3898", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/db3a9ba195ec4b5385f2c415ce1f4720.json"}}], "type": "peer-review", "published": "2019-06-19", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.46267.038", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:52:48.660Z", "modified": "2026-08-20T13:52:48.720Z"}, {"entity": "publication", "iuid": "29364defa7344e85803c5a50536254b9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/29364defa7344e85803c5a50536254b9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/29364defa7344e85803c5a50536254b9"}}, "title": "Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite", "authors": [{"family": "Andersson", "given": "Annika", "initials": "A"}, {"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}, {"family": "Magoulopoulou", "given": "Anastasia", "initials": "A"}, {"family": "Lejarre", "given": "Quentin", "initials": "Q"}, {"family": "Lara", "given": "Patricia", "initials": "P"}, {"family": "Xu", "given": "Peibo", "initials": "P"}, {"family": "Goel", "given": "Suchi", "initials": "S"}, {"family": "Pissi", "given": "Jennifer", "initials": "J"}, {"family": "Ru", "given": "Xing", "initials": "X"}, {"family": "Hessa", "given": "Tara", "initials": "T"}, {"family": "Wahlgren", "given": "Mats", "initials": "M"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Nilsson", "given": "IngMarie", "initials": "I", "orcid": "0000-0002-7981-3201", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9df508868ae34871b53cec2d912dd44a.json"}}, {"family": "Tellgren-Roth", "given": "\u00c5sa", "initials": "\u00c5"}], "type": "posted-content", "published": "2019-05-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/653998", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:53.210Z", "modified": "2026-08-20T11:13:53.278Z"}, {"entity": "publication", "iuid": "5ad7d6b43851434ab564834089559d4b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5ad7d6b43851434ab564834089559d4b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5ad7d6b43851434ab564834089559d4b"}}, "title": "Cotranslational folding cooperativity of contiguous domains of \u03b1-spectrin", "authors": [{"family": "Kemp", "given": "Grant", "initials": "G", "orcid": "0000-0001-5125-2740", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d715b8af2972418aa144b2ca11487ce4.json"}}, {"family": "Nilsson", "given": "Ola B", "initials": "OB"}, {"family": "Tian", "given": "Pengfei", "initials": "P"}, {"family": "Best", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7893-3543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36c5cc15e14e412fb8798666bd48f00f.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2019-05-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/653360", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:51.259Z", "modified": "2026-08-20T11:13:51.326Z"}, {"entity": "publication", "iuid": "840683b953bf44e1ae623f117e0ebbcd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/840683b953bf44e1ae623f117e0ebbcd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/840683b953bf44e1ae623f117e0ebbcd"}}, "title": "Detecting Novel Sequence Signals in Targeting Peptides Using Deep Learning", "authors": [{"family": "Almagro Armenteros", "given": "J J", "initials": "JJ"}, {"family": "Salvatore", "given": "M", "initials": "M"}, {"family": "Emanuelsson", "given": "O", "initials": "O", "orcid": "0000-0002-8879-9245", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a51c22f2bc594fe3a349bec5363f394f.json"}}, {"family": "Winther", "given": "O", "initials": "O"}, {"family": "von Heijne", "given": "G", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Elofsson", "given": "A", "initials": "A", "orcid": "0000-0002-7115-9751", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/248e70e81bd64f31a5f83e6e329bba95.json"}}, {"family": "Nielsen", "given": "H", "initials": "H"}], "type": "posted-content", "published": "2019-05-17", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/639203", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:47.748Z", "modified": "2026-08-20T11:13:47.788Z"}, {"entity": "publication", "iuid": "0c4ed5309a014ed2912fe7f6df05a3c7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0c4ed5309a014ed2912fe7f6df05a3c7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0c4ed5309a014ed2912fe7f6df05a3c7"}}, "title": "Dynamic membrane topology in an unassembled membrane protein", "authors": [{"family": "Seurig", "given": "Maximilian", "initials": "M"}, {"family": "Ek", "given": "Moira", "initials": "M"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Fluman", "given": "Nir", "initials": "N", "orcid": "0000-0001-9909-0779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4877a1d13c864bdf88de5bc383750994.json"}}], "type": "posted-content", "published": "2019-02-13", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/548537", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:12:18.614Z", "modified": "2026-08-20T11:12:18.635Z"}, {"entity": "publication", "iuid": "3d2666aeab594f11941415b21465d48d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3d2666aeab594f11941415b21465d48d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3d2666aeab594f11941415b21465d48d"}}, "title": "The shape of the bacterial ribosome exit tunnel affects cotranslational protein folding.", "authors": [{"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}, {"family": "Tian", "given": "Pengfei", "initials": "P"}, {"family": "Pardo-Avila", "given": "F\u00e1tima", "initials": "F"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55fa4ba347a34d7ca80d214e8d718e44.json"}}, {"family": "Best", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7893-3543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36c5cc15e14e412fb8798666bd48f00f.json"}}, {"family": "Bernstein", "given": "Harris D", "initials": "HD", "orcid": "0000-0002-4941-3741", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb6371b33ef4475083cedc5d0a0fe8c4.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2018-11-26", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "7", "issn-l": "2050-084X"}, "abstract": "The E. coli ribosome exit tunnel can accommodate small folded proteins, while larger ones fold outside. It remains unclear, however, to what extent the geometry of the tunnel influences protein folding. Here, using E. coli ribosomes with deletions in loops in proteins uL23 and uL24 that protrude into the tunnel, we investigate how tunnel geometry determines where proteins of different sizes fold. We find that a 29-residue zinc-finger domain normally folding close to the uL23 loop folds deeper in the tunnel in uL23 \u0394loop ribosomes, while two ~ 100 residue proteins normally folding close to the uL24 loop near the tunnel exit port fold at deeper locations in uL24 \u0394loop ribosomes, in good agreement with results obtained by coarse-grained molecular dynamics simulations. This supports the idea that cotranslational folding commences once a protein domain reaches a location in the exit tunnel where there is sufficient space to house the folded structure.", "doi": "10.7554/eLife.36326", "pmid": "30475203", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6298777"}, {"db": "pii", "key": "36326"}], "notes": [], "created": "2026-08-20T13:52:24.997Z", "modified": "2026-08-20T13:52:25.126Z"}, {"entity": "publication", "iuid": "49cdef8c317540d48847ac6f8921b6c5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/49cdef8c317540d48847ac6f8921b6c5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/49cdef8c317540d48847ac6f8921b6c5"}}, "title": "Force-profile analysis of the cotranslational folding of HemK and filamin domains: Comparison of biochemical and biophysical folding assays", "authors": [{"family": "Kemp", "given": "Grant", "initials": "G"}, {"family": "Kudva", "given": "Renuka", "initials": "R"}, {"family": "Rosa", "given": "Andr\u00e9s de la", "initials": "Adl"}, {"family": "Heijne", "given": "Gunnar von", "initials": "Gv", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2018-11-15", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/470831", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:11:30.306Z", "modified": "2026-08-20T11:11:30.355Z"}, {"entity": "publication", "iuid": "8d2ed4697f3240fb81ed45c946f120e2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8d2ed4697f3240fb81ed45c946f120e2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8d2ed4697f3240fb81ed45c946f120e2"}}, "title": "Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome.", "authors": [{"family": "Far\u00edas-Rico", "given": "Jos\u00e9 Arcadio", "initials": "JA", "orcid": "0000-0002-9168-6305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4d71db1b0ce4083aa92f31dfb391cf5.json"}}, {"family": "Ruud Selin", "given": "Frida", "initials": "F"}, {"family": "Myronidi", "given": "Ioanna", "initials": "I"}, {"family": "Fr\u00fchauf", "given": "Marie", "initials": "M"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "journal article", "published": "2018-10-02", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "115", "issue": "40", "pages": "E9280-E9287", "issn-l": "0027-8424"}, "abstract": "During the last five decades, studies of protein folding in dilute buffer solutions have produced a rich picture of this complex process. In the cell, however, proteins can start to fold while still attached to the ribosome (cotranslational folding) and it is not yet clear how the ribosome affects the folding of protein domains of different sizes, thermodynamic stabilities, and net charges. Here, by using arrest peptides as force sensors and on-ribosome pulse proteolysis, we provide a comprehensive picture of how the distance from the peptidyl transferase center in the ribosome at which proteins fold correlates with protein size. Moreover, an analysis of a large collection of mutants of the Escherichia coli ribosomal protein S6 shows that the force exerted on the nascent chain by protein folding varies linearly with the thermodynamic stability of the folded state, and that the ribosome environment disfavors folding of domains of high net-negative charge.", "doi": "10.1073/pnas.1812756115", "pmid": "30224455", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6176590"}, {"db": "pii", "key": "1812756115"}], "notes": [], "created": "2026-08-20T09:30:05.604Z", "modified": "2026-08-20T09:30:05.658Z"}, {"entity": "publication", "iuid": "cfb2a1f4aaf94da59ddda22ae2c8f22e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cfb2a1f4aaf94da59ddda22ae2c8f22e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cfb2a1f4aaf94da59ddda22ae2c8f22e"}}, "title": "Author response: The shape of the bacterial ribosome exit tunnel affects cotranslational protein folding", "authors": [{"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8f164c44cca4540965f66c2829f624e.json"}}, {"family": "Tian", "given": "Pengfei", "initials": "P"}, {"family": "Pardo-Avila", "given": "F\u00e1tima", "initials": "F"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55fa4ba347a34d7ca80d214e8d718e44.json"}}, {"family": "Best", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7893-3543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36c5cc15e14e412fb8798666bd48f00f.json"}}, {"family": "Bernstein", "given": "Harris D", "initials": "HD", "orcid": "0000-0002-4941-3741", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb6371b33ef4475083cedc5d0a0fe8c4.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "peer-review", "published": "2018-06-13", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.36326.028", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:52:27.102Z", "modified": "2026-08-20T13:52:27.148Z"}, {"entity": "publication", "iuid": "72f10fe47f2e4fbd964e4856e4c19de9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/72f10fe47f2e4fbd964e4856e4c19de9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/72f10fe47f2e4fbd964e4856e4c19de9"}}, "title": "Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome", "authors": [{"family": "Far\u00edas-Rico", "given": "Jos\u00e9 Arcadio", "initials": "JA", "orcid": "0000-0002-9168-6305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4d71db1b0ce4083aa92f31dfb391cf5.json"}}, {"family": "Selin", "given": "Frida Ruud", "initials": "FR"}, {"family": "Myronidi", "given": "Ioanna", "initials": "I"}, {"family": "Fr\u00fchauf", "given": "Marie", "initials": "M"}, {"family": "Heijne", "given": "Gunnar von", "initials": "Gv", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2018-04-18", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/303784", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:10:03.639Z", "modified": "2026-08-20T11:10:03.699Z"}, {"entity": "publication", "iuid": "65fee0d304a44870b883cdba7fb17788", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/65fee0d304a44870b883cdba7fb17788.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/65fee0d304a44870b883cdba7fb17788"}}, "title": "Cotranslational folding of a pentarepeat \u03b2-helix protein", "authors": [{"family": "Notari", "given": "Luigi", "initials": "L"}, {"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M"}, {"family": "Farias-Rico", "given": "Jose Arcadio", "initials": "JA"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2018-01-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/255810", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:09:28.467Z", "modified": "2026-08-20T11:09:28.521Z"}, {"entity": "publication", "iuid": "53f0fa8aa82049cebefa26f3421de549", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/53f0fa8aa82049cebefa26f3421de549.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/53f0fa8aa82049cebefa26f3421de549"}}, "title": "Mutational analysis of the human Xbp1 translational arrest peptide and construction of arrest-enhanced variants", "authors": [{"family": "Schiller", "given": "Nina", "initials": "N"}, {"family": "Magoulopoulou", "given": "Anastasia", "initials": "A"}, {"family": "Cymer", "given": "Florian", "initials": "F"}, {"family": "Von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2017-10-11", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/201913", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:55:17.585Z", "modified": "2026-08-20T09:55:17.637Z"}, {"entity": "publication", "iuid": "3e4caba97eb24ac9a31eb47d822bf0b9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3e4caba97eb24ac9a31eb47d822bf0b9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3e4caba97eb24ac9a31eb47d822bf0b9"}}, "title": "Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide.", "authors": [{"family": "Snapp", "given": "Erik Lee", "initials": "EL"}, {"family": "McCaul", "given": "Nicholas", "initials": "N"}, {"family": "Quandte", "given": "Matthias", "initials": "M"}, {"family": "Cabartova", "given": "Zuzana", "initials": "Z"}, {"family": "Bontjer", "given": "Ilja", "initials": "I"}, {"family": "K\u00e4llgren", "given": "Carolina", "initials": "C"}, {"family": "Nilsson", "given": "IngMarie", "initials": "I"}, {"family": "Land", "given": "Aafke", "initials": "A"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Sanders", "given": "Rogier W", "initials": "RW"}, {"family": "Braakman", "given": "Ineke", "initials": "I", "orcid": "0000-0003-1592-4364", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3178e3523e1a499c87575360fc2f483b.json"}}], "type": "journal article", "published": "2017-07-28", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "6", "issue": null, "issn-l": "2050-084X"}, "abstract": "Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is targeted to the endoplasmic reticulum (ER) by its signal peptide during synthesis. Proper gp160 folding in the ER requires core glycosylation, disulfide-bond formation and proline isomerization. Signal-peptide cleavage occurs only late after gp160 chain termination and is dependent on folding of the soluble subunit gp120 to a near-native conformation. We here detail the mechanism by which co-translational signal-peptide cleavage is prevented. Conserved residues from the signal peptide and residues downstream of the canonical cleavage site form an extended alpha-helix in the ER membrane, which covers the cleavage site, thus preventing cleavage. A point mutation in the signal peptide breaks the alpha helix allowing co-translational cleavage. We demonstrate that postponed cleavage of gp160 enhances functional folding of the molecule. The change to early cleavage results in decreased viral fitness compared to wild-type HIV.", "doi": "10.7554/eLife.26067", "pmid": "28753126", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pmc", "key": "PMC5577925"}, {"db": "pii", "key": "26067"}], "notes": [], "created": "2018-12-05T12:28:13.894Z", "modified": "2026-08-20T13:52:14.842Z"}, {"entity": "publication", "iuid": "ed04b18dce73428dad17d765f3afb01d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ed04b18dce73428dad17d765f3afb01d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ed04b18dce73428dad17d765f3afb01d"}}, "title": "Author response: Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide", "authors": [{"family": "Snapp", "given": "Erik Lee", "initials": "EL"}, {"family": "McCaul", "given": "Nicholas", "initials": "N"}, {"family": "Quandte", "given": "Matthias", "initials": "M"}, {"family": "Cabartova", "given": "Zuzana", "initials": "Z"}, {"family": "Bontjer", "given": "Ilja", "initials": "I"}, {"family": "K\u00e4llgren", "given": "Carolina", "initials": "C"}, {"family": "Nilsson", "given": "IngMarie", "initials": "I"}, {"family": "Land", "given": "Aafke", "initials": "A"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Sanders", "given": "Rogier W", "initials": "RW"}, {"family": "Braakman", "given": "Ineke", "initials": "I", "orcid": "0000-0003-1592-4364", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3178e3523e1a499c87575360fc2f483b.json"}}], "type": "peer-review", "published": "2017-07-21", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.26067.018", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:52:16.876Z", "modified": "2026-08-20T13:52:16.939Z"}, {"entity": "publication", "iuid": "9e3d9eb161254546b2717d84a66f73fe", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9e3d9eb161254546b2717d84a66f73fe.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9e3d9eb161254546b2717d84a66f73fe"}}, "title": "The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling.", "authors": [{"family": "Su", "given": "Ting", "initials": "T", "orcid": "0000-0002-3185-8144", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d496e2bc5d34090a8454c553a7f21ea.json"}}, {"family": "Cheng", "given": "Jingdong", "initials": "J", "orcid": "0000-0003-4442-377X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d20d179bb3b4727a94304aab9401e84.json"}}, {"family": "Sohmen", "given": "Daniel", "initials": "D"}, {"family": "Hedman", "given": "Rickard", "initials": "R"}, {"family": "Berninghausen", "given": "Otto", "initials": "O"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7c2d78750ccb42239a7363f99f58dcc5.json"}}, {"family": "Beckmann", "given": "Roland", "initials": "R", "orcid": "0000-0003-4291-3898", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/db3a9ba195ec4b5385f2c415ce1f4720.json"}}], "type": "journal article", "published": "2017-05-30", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "6", "issue": null, "issn-l": "2050-084X"}, "abstract": "Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 \u00c5 cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two \u03b1-helices connected by an \u03b1-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50-55 \u00c5 of the exit tunnel. The structure reveals how \u03b1-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome.", "doi": "10.7554/eLife.25642", "pmid": "28556777", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pmc", "key": "PMC5449182"}, {"db": "pii", "key": "e25642"}], "notes": [], "created": "2018-12-05T11:26:11.770Z", "modified": "2026-08-20T13:52:08.671Z"}, {"entity": "publication", "iuid": "9a237cc1cea04e4db61963c8b08b68de", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9a237cc1cea04e4db61963c8b08b68de.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9a237cc1cea04e4db61963c8b08b68de"}}, "title": "Author response: The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling", "authors": [{"family": "Su", "given": "Ting", "initials": "T", "orcid": "0000-0002-3185-8144", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d496e2bc5d34090a8454c553a7f21ea.json"}}, {"family": "Cheng", "given": "Jingdong", "initials": "J", "orcid": "0000-0003-4442-377X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d20d179bb3b4727a94304aab9401e84.json"}}, {"family": "Sohmen", "given": "Daniel", "initials": "D"}, {"family": "Hedman", "given": "Rickard", "initials": "R"}, {"family": "Berninghausen", "given": "Otto", "initials": "O"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7c2d78750ccb42239a7363f99f58dcc5.json"}}, {"family": "Beckmann", "given": "Roland", "initials": "R", "orcid": "0000-0003-4291-3898", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/db3a9ba195ec4b5385f2c415ce1f4720.json"}}], "type": "peer-review", "published": "2017-05-17", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.25642.017", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:52:10.571Z", "modified": "2026-08-20T13:52:10.616Z"}, {"entity": "publication", "iuid": "caba2e0f2abe42e990e8bb3d4baa9651", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/caba2e0f2abe42e990e8bb3d4baa9651.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/caba2e0f2abe42e990e8bb3d4baa9651"}}, "title": "Stable membrane topologies of small dual-topology membrane proteins", "authors": [{"family": "Fluman", "given": "Nir", "initials": "N", "orcid": "0000-0001-9909-0779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4877a1d13c864bdf88de5bc383750994.json"}}, {"family": "Tobiasson", "given": "Victor", "initials": "V"}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/529a460e668a479ca7d9b9271375ef9f.json"}}], "type": "posted-content", "published": "2017-05-02", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/133298", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:54:22.495Z", "modified": "2026-08-20T09:54:22.552Z"}]}