Nucleation seed size determines amyloid clearance and establishes a barrier to prion appearance in yeast
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Final Accepted Manuscript
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Univ Arizona, Dept Mol & Cellular BiolIssue Date
2020-05-04
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NATURE PUBLISHING GROUPCitation
Villali, J., Dark, J., Brechtel, T.M. et al. Nucleation seed size determines amyloid clearance and establishes a barrier to prion appearance in yeast. Nat Struct Mol Biol (2020). https://doi.org/10.1038/s41594-020-0416-6Rights
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2020.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Amyloid appearance is a rare event that is promoted in the presence of other aggregated proteins. These aggregates were thought to act by templating the formation of an assembly-competent nucleation seed, but we find an unanticipated role for them in enhancing the persistence of amyloid after it arises. Specifically, Saccharomyces cerevisiae Rnq1 amyloid reduces chaperone-mediated disassembly of Sup35 amyloid, promoting its persistence in yeast. Mathematical modeling and corresponding in vivo experiments link amyloid persistence to the conformationally defined size of the Sup35 nucleation seed and suggest that amyloid is actively cleared by disassembly below this threshold to suppress appearance of the [PSI+] prion in vivo. Remarkably, this framework resolves multiple known inconsistencies in the appearance and curing of yeast prions. Thus, our observations establish the size of the nucleation seed as a previously unappreciated characteristic of prion variants that is key to understanding transitions between prion states.Note
6 month embargo; published online: 4 May 2020ISSN
1545-9993EISSN
1545-9985PubMed ID
32367069Version
Final accepted manuscriptae974a485f413a2113503eed53cd6c53
10.1038/s41594-020-0416-6