{"entity": "researcher", "timestamp": "2026-08-20T20:47:14.307Z", "family": "Nicolaus", "given": "Felix", "initials": "F", "orcid": "0000-0001-9230-8544", "affiliations": ["Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f47078a41e242c98a1b2a3c2ad0ebe9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f47078a41e242c98a1b2a3c2ad0ebe9"}}, "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": "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": "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": "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"}]}