Nucleation seed size determines amyloid clearance and establishes a barrier to prion appearance in yeast
AffiliationUniv Arizona, Dept Mol & Cellular Biol
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationVillali, 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/s41594-020-0416-6
Rights© The Author(s), under exclusive licence to Springer Nature America, Inc. 2020
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AbstractAmyloid 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.
Note6 month embargo; published online: 4 May 2020
VersionFinal accepted manuscript
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