{"entity": "publication", "iuid": "cddad9583da743ca99f4f837e46f08d5", "timestamp": "2026-08-20T20:49:03.127Z", "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"}