Structural and dynamical determinants of a β-sheet-enriched intermediate involved in amyloid fibrillar assembly of human prion protein.

ABSTRACT: The conformational conversion of the cellular prion protein (PrP^C) into a misfolded, aggregated and infectious scrapie isoform is associated with prion disease pathology and neurodegeneration. Despite the significant number of experimental and theoretical studies the molecular mechanism regulating this structural transition is still poorly understood. Here, via Nuclear Magnetic Resonance (NMR) methodologies we investigate at the atomic level the mechanism of the human HuPrP(90-231) thermal unfolding and characterize the conformational equilibrium between its native structure and a β-enriched intermediate state, named β-PrPI. By comparing the folding mechanisms of metal-free and Cu²⁺-bound HuPrP(23-231) and HuPrP(90-231) we show that the coupling between the N-

SUBMITTER: Russo L 

PROVIDER: S-EPMC9473526 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature