Exposed Hsp70-binding site impacts yeast Sup35 prion disaggregation and propagation.

ABSTRACT: The dynamic balance between formation and disaggregation of amyloid fibrils is associated with many neurodegenerative diseases. Multiple chaperones interact with and disaggregate amyloid fibrils, which impacts amyloid propagation and cellular phenotypes. However, it remains poorly understood whether and how site-specific binding of chaperones to amyloids facilitates the concerted disaggregation process and modulates physiological consequences in vivo. Here, we identified binding sites of Ssa1, Sis1, and Hsp104 chaperones for Sup35, the protein determinant of yeast prion [PSI⁺] yeast. Our biophysical and genetic analyses with various Sup35 deletion mutants and amyloid conformations revealed that the Ssa1-binding to the region outside amyloid core plays a key role in facili

SUBMITTER: Shen CH 

PROVIDER: S-EPMC11665907 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature