Nucleation Seed Size Determines Amyloid Clearance and Establishes a Barrier to Prion Appearance in Yeast

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2020 May 6

PMID 32367069

Citations 15

Authors

Janice Villali

Jason Dark

Teal M Brechtel

Fen Pei

Suzanne S Sindi

Tricia R Serio

Affiliations

Soon will be listed here.

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.

Citing Articles

Multiple aspects of amyloid dynamics integrate to establish prion variant dominance in yeast.

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