Liquid-liquid phase separation of full-length prion protein initiates conformational conversion in vitro.

ABSTRACT: Prion diseases are characterized by the accumulation of amyloid fibrils. The causative agent is an infectious amyloid that comprises solely misfolded prion protein (PrP^Sc). Prions can convert normal cellular prion protein (PrP^C) to protease K-resistance prion protein fragment (PrP-res) in vitro; however, the intermediate steps involved in this spontaneous conversion still remain unknown. We investigated whether recombinant prion protein (rPrP) can directly convert into PrP-res via liquid-liquid phase separation (LLPS) in the absence of PrP^Sc. We found that rPrP underwent LLPS at the interface of the aqueous two-phase system of polyethylene glycol and dextran, whereas single-phase conditions were not inducible. Fluorescence recovery assay after photobleachin

SUBMITTER: Tange H 

PROVIDER: S-EPMC8289115 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature