{"entity": "researcher", "timestamp": "2026-10-13T19:35:13.404Z", "family": "Kozielewicz", "given": "Pawe\u0142", "initials": "P", "orcid": "0000-0003-1414-3566", "affiliations": [], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b"}}, "publications": [{"entity": "publication", "iuid": "a243894c93604eeca7d58ee0af53d8a2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a243894c93604eeca7d58ee0af53d8a2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a243894c93604eeca7d58ee0af53d8a2"}}, "title": "SAG1.3-derived Frizzled-targeting negative allosteric modulators", "authors": [{"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}, {"family": "Gr\u00e4tz", "given": "Lukas", "initials": "L", "orcid": "0000-0001-6755-0742", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/336fa12649bb40c99a66334c74a2a91b.json"}}, {"family": "Turku", "given": "Ainoleena", "initials": "A", "orcid": "0000-0003-0959-7221", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/80fbb027505240eaaebf4153df67a47f.json"}}, {"family": "Kozielewicz", "given": "Pawel", "initials": "P", "orcid": "0000-0003-1414-3566", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b.json"}}, {"family": "Bowin", "given": "Carl Fredrik", "initials": "CF", "orcid": "0000-0001-9090-9493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4af507d21b5d4b4b938f3f6888d95075.json"}}, {"family": "Scharf", "given": "Magdalena", "initials": "M", "orcid": "0000-0002-3305-3956", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca43ba6516014fe597ead17e737f697a.json"}}, {"family": "Voss", "given": "Jan", "initials": "J"}, {"family": "Kinsolving", "given": "Julia", "initials": "J"}, {"family": "Shekhani", "given": "Rawan", "initials": "R"}, {"family": "Oliva-Vilarnau", "given": "Nuria", "initials": "N"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "K\u00f6rber", "given": "Marlies", "initials": "M"}, {"family": "Lauschke", "given": "Volker", "initials": "V", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}, {"family": "L\u00f6ber", "given": "Stefan", "initials": "S"}, {"family": "Gmeiner", "given": "Peter", "initials": "P", "orcid": "0000-0002-4127-197X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f9c6990db94493f902488530f54636c.json"}}], "type": "posted-content", "published": "2024-02-20", "journal": {"issn-l": null}, "abstract": null, "doi": "10.21203/rs.3.rs-3910794/v1", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-09-23T15:32:12.796Z", "modified": "2026-09-23T15:32:12.921Z"}, {"entity": "publication", "iuid": "a1f4420f0fe54419acb90d1042a2f9d7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a1f4420f0fe54419acb90d1042a2f9d7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a1f4420f0fe54419acb90d1042a2f9d7"}}, "title": "Pathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations.", "authors": [{"family": "Gr\u00e4tz", "given": "Lukas", "initials": "L", "orcid": "0000-0001-6755-0742", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/336fa12649bb40c99a66334c74a2a91b.json"}}, {"family": "Kowalski-Jahn", "given": "Maria", "initials": "M", "orcid": "0000-0003-1442-3656", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a23a8e0b2e8543b68098981fd39d97b6.json"}}, {"family": "Scharf", "given": "Magdalena M", "initials": "MM", "orcid": "0000-0002-3305-3956", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca43ba6516014fe597ead17e737f697a.json"}}, {"family": "Kozielewicz", "given": "Pawel", "initials": "P", "orcid": "0000-0003-1414-3566", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b.json"}}, {"family": "Jahn", "given": "Michael", "initials": "M", "orcid": "0000-0002-3913-153X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce2ef4c47b24946876c12a549785e36.json"}}, {"family": "Bous", "given": "Julien", "initials": "J", "orcid": "0000-0002-3459-7592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/435ffe2f8b11423f8d68fc41c0d4171c.json"}}, {"family": "Lambert", "given": "Nevin A", "initials": "NA", "orcid": "0000-0001-7550-0921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56c24f300f0142de983b18f22352e2fe.json"}}, {"family": "Gloriam", "given": "David E", "initials": "DE", "orcid": "0000-0002-4299-7561", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d4cf683c6874e7782c68b00d38b926c.json"}}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}], "type": "journal article", "published": "2023-07-29", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "4573", "issn-l": "2041-1723"}, "abstract": "The class Frizzled of G protein-coupled receptors (GPCRs), consisting of ten Frizzled (FZD1-10) paralogs and Smoothened, remains one of the most enigmatic GPCR families. This class mediates signaling predominantly through Disheveled (DVL) or heterotrimeric G proteins. However, the mechanisms underlying pathway selection are elusive. Here we employ a structure-driven mutagenesis approach in combination with an extensive panel of functional signaling readouts to investigate the importance of conserved state-stabilizing residues in FZD5 for signal specification. Similar data were obtained for FZD4 and FZD10 suggesting that our findings can be extrapolated to other members of the FZD family. Comparative molecular dynamics simulations of wild type and selected FZD5 mutants further support the concept that distinct conformational changes in FZDs specify the signal outcome. In conclusion, we find that FZD5 and FZDs in general prefer coupling to DVL rather than heterotrimeric G proteins and that distinct active state micro-switches in the receptor are essential for pathway selection arguing for conformational changes in the receptor protein defining transducer selectivity.", "doi": "10.1038/s41467-023-40213-0", "pmid": "37516754", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10387068"}, {"db": "pii", "key": "10.1038/s41467-023-40213-0"}], "notes": [], "created": "2026-08-21T11:49:27.881Z", "modified": "2026-09-23T10:46:35.285Z"}, {"entity": "publication", "iuid": "1ccddc0c63f34f59a08b278111e9dbef", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1ccddc0c63f34f59a08b278111e9dbef.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1ccddc0c63f34f59a08b278111e9dbef"}}, "title": "A conserved molecular switch in Class F receptors regulates receptor activation and pathway selection.", "authors": [{"family": "Wright", "given": "Shane C", "initials": "SC", "orcid": "0000-0002-7470-5068", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bb883060bdc45ddb27b4d4f737de17e.json"}}, {"family": "Kozielewicz", "given": "Pawe\u0142", "initials": "P", "orcid": "0000-0003-1414-3566", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b.json"}}, {"family": "Kowalski-Jahn", "given": "Maria", "initials": "M"}, {"family": "Petersen", "given": "Julian", "initials": "J"}, {"family": "Bowin", "given": "Carl-Fredrik", "initials": "CF"}, {"family": "Slodkowicz", "given": "Greg", "initials": "G"}, {"family": "Marti-Solano", "given": "Maria", "initials": "M", "orcid": "0000-0003-0373-8927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2724e93722494fb28214cbbe0bd8c499.json"}}, {"family": "Rodr\u00edguez", "given": "David", "initials": "D"}, {"family": "Hot", "given": "Belma", "initials": "B"}, {"family": "Okashah", "given": "Najeah", "initials": "N"}, {"family": "Strakova", "given": "Katerina", "initials": "K"}, {"family": "Valnohova", "given": "Jana", "initials": "J"}, {"family": "Babu", "given": "M Madan", "initials": "MM", "orcid": "0000-0003-0556-6196", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/86a83ee050b44075b722c6df37192df9.json"}}, {"family": "Lambert", "given": "Nevin A", "initials": "NA", "orcid": "0000-0001-7550-0921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56c24f300f0142de983b18f22352e2fe.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J"}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}], "type": "journal article", "published": "2019-02-08", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "10", "issue": "1", "pages": "667"}, "abstract": "Class F receptors are considered valuable therapeutic targets due to their role in human disease, but structural changes accompanying receptor activation remain unexplored. Employing population and cancer genomics data, structural analyses, molecular dynamics simulations, resonance energy transfer-based approaches and mutagenesis, we identify a conserved basic amino acid in TM6 in Class F receptors that acts as a molecular switch to mediate receptor activation. Across all tested Class F receptors (FZD4,5,6,7, SMO), mutation of the molecular switch confers an increased potency of agonists by stabilizing an active conformation as assessed by engineered mini G proteins as conformational sensors. Disruption of the switch abrogates the functional interaction between FZDs and the phosphoprotein Dishevelled, supporting conformational selection as a prerequisite for functional selectivity. Our studies reveal the molecular basis of a common activation mechanism conserved in all Class F receptors, which facilitates assay development and future discovery of Class F receptor-targeting drugs.", "doi": "10.1038/s41467-019-08630-2", "pmid": "30737406", "labels": {"Jens Carlsson": "", "SciLifeLab Fellow": ""}, "xrefs": [{"db": "pmc", "key": "PMC6368630"}, {"db": "pii", "key": "10.1038/s41467-019-08630-2"}], "notes": [], "created": "2020-09-29T13:54:35.809Z", "modified": "2026-09-23T09:12:54.034Z"}]}