Structure of prion β-oligomers as determined by short-distance crosslinking constraint-guided discrete molecular dynamics simulations.

ABSTRACT: The conversion of the native monomeric cellular prion protein (PrP^C ) into an aggregated pathological β-oligomeric form (PrP^β ) and an infectious form (PrP^Sc ) is the central element in the development of prion diseases. The structure of the aggregates and the molecular mechanisms of the conformational changes involved in the conversion are still unknown. We applied mass spectrometry combined with chemical crosslinking, hydrogen/deuterium exchange, limited proteolysis, and surface modification for the differential characterization of the native and the urea+acid-converted prion β-oligomer structures to obtain insights into the mechanisms of conversion and aggregation. For the determination of the structure of the monomer and the dimer unit of the β-oligomer

SUBMITTER: Serpa JJ 

PROVIDER: S-EPMC9285417 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature