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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Protein intrinsically disordered regions (IDRs) play important biological roles despite lacking stable structures. IDRs drive the formation of both biomolecular condensates via liquid\u2013liquid phase separation (LLPS) and solid fibrous amyloid aggregates. Amyloids can be pathogenic and may exhibit self-perpetuating (prion) properties. Relationships between LLPS and the amyloid-forming and prion-propagating abilities of IDRs remain poorly understood. The N-proximal IDR of the yeast translation termination factor eRF3 (Sup35) can form both liquid condensates and heritable amyloid-based prions and serves as a powerful model for investigating these phenomena due to the availability of simple phenotypic, cytological and biochemical assays. Deletion analysis demonstrates that the N-proximal prion domain (Sup35N) of Sup35 is sufficient for chaperone-dependent prion propagation and that various regions of this domain show differential impacts on LLPS, amyloid aggregation, and prion inheritance. Specifically, the N-terminal NQ-rich stretch and the region of oligopeptide repeats are the most important contributors to the LLPS and formation of amyloid fibrils, while oligopeptide repeats and the C-terminal region of Sup35N are crucial for prion inheritance. Contrary to previous reports, the NQ-rich stretch is not required for prion formation and inheritance in yeast. Our data indicate that, in addition to amino acid composition, specific sequence motifs control reversible and heritable assemblies of Sup35.<\/jats:p>","DOI":"10.3390\/ijms27177516","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion Analysis of Phase Separation, Amyloid Formation and Prion Propagation by the Intrinsically Disordered Region of Yeast Sup35 Protein"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-8171","authenticated-orcid":false,"given":"Anastasia V.","family":"Grizel","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Krone EBB, 950 Atlantic Dr. NW, Atlanta, GA 30332-2000, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia A.","family":"Gorsheneva","sequence":"additional","affiliation":[{"name":"Laboratory of Amyloid Biology, St. Petersburg State University, 7\/9 Universitetskaya emb, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8225-5661","authenticated-orcid":false,"given":"Ismat Jahan","family":"Anee","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Krone EBB, 950 Atlantic Dr. NW, Atlanta, GA 30332-2000, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristupas","family":"Paulius","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Krone EBB, 950 Atlantic Dr. NW, Atlanta, GA 30332-2000, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-4560","authenticated-orcid":false,"given":"Konstantin Y.","family":"Kulichikhin","sequence":"additional","affiliation":[{"name":"Laboratory of Amyloid Biology, St. Petersburg State University, 7\/9 Universitetskaya emb, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-2006","authenticated-orcid":false,"given":"Aleksandr A.","family":"Rubel","sequence":"additional","affiliation":[{"name":"Laboratory of Amyloid Biology, St. Petersburg State University, 7\/9 Universitetskaya emb, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-9051","authenticated-orcid":false,"given":"Yury O.","family":"Chernoff","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Krone EBB, 950 Atlantic Dr. NW, Atlanta, GA 30332-2000, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41580-023-00673-0","article-title":"The molecular basis for cellular function of intrinsically disordered protein regions","volume":"25","author":"Holehouse","year":"2024","journal-title":"Nat. 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