Liquid and Hydrogel Phases of PrP^C Linked to Conformation Shifts and Triggered by Alzheimer's Amyloid-β Oligomers.

ABSTRACT: Protein phase separation by low-complexity, intrinsically disordered domains generates membraneless organelles and links to neurodegeneration. Cellular prion protein (PrP^C) contains such domains, causes spongiform degeneration, and is a receptor for Alzheimer's amyloid-β oligomers (Aβo). Here, we show that PrP^C separates as a liquid phase, in which α-helical Thr become unfolded. At the cell surface, PrP^C Lys residues interact with Aβo to create a hydrogel containing immobile Aβo and relatively mobile PrP^C. The Aβo/PrP hydrogel has a well-defined stoichiometry and dissociates with excess Aβo. NMR studies of hydrogel PrP^C reveal a distinct α-helical conformation for natively unfolded amino-terminal Gly and Ala residues. Aβo/PrP hydrogel

SUBMITTER: Kostylev MA 

PROVIDER: S-EPMC6226277 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature