Role of the Disulfide Bond in Prion Protein Amyloid Formation: A Thermodynamic and Kinetic Analysis.

ABSTRACT: Prion diseases are associated with the structural conversion of prion protein (PrP) to a β-sheet-rich aggregate, PrP^Sc. Previous studies have indicated that a reduction of the disulfide bond linking C179 and C214 of PrP yields an amyloidlike β-rich aggregate in vitro. To gain mechanistic insights into the reduction-induced aggregation, here I characterized how disulfide bond reduction modulates the protein folding/misfolding landscape of PrP, by examining 1) the equilibrium stabilities of the native (N) and aggregated states relative to the unfolded (U) state, 2) the transition barrier separating the U and aggregated states, and 3) the final structure of amyloidlike misfolded aggregates. Kinetic and thermodynamic experiments revealed that disulfide bond reduction decreases the e

SUBMITTER: Honda R 

PROVIDER: S-EPMC5984966 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature