Cellular Prion Protein Conformational Shift after Liquid-Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations.

ABSTRACT: Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins has been associated with neurodegenerative diseases, although direct mechanisms are poorly defined. Here, we report on a maturation process for the cellular prion protein (PrP^C) that involves a conformational change after LLPS and is regulated by mutations and poly(4-styrenesulfonic acid-co-maleic acid) (PSCMA), a molecule that has been reported to rescue Alzheimer's disease-related cognitive deficits by antagonizing the interaction between PrP^C and amyloid-β oligomers (Aβo). We show that PSCMA can induce reentrant LLPS of PrP^C and lower the saturation concentration (C_sat) of PrP^C by 100-fold. Regardless of the induction method, PrP^C mol

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11469297 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature