Transient multimers modulate conformer abundances of prion protein monomer through conformational selection.

ABSTRACT: Prions are known to be involved in neurodegenerative pathologies such as Creutzfeld-Jakob disease. Current models point to a molecular event which rely on a transmissible structural change that leads to the production of β-sheet-rich prion conformer (PrP^Sc). PrP^Sc itself has the capability to trigger the structural rearrangement of the ubiquitously present prion (PrP^c) substrate in a self-perpetuating cascade. In this article, we demonstrate that recombinant PrP^c exists in a conformational equilibrium. The conformers' abundances were shown to be dependent on PrP^c concentration through the formation of transient multimers leading to conformational selection. The study of PrP^c mutants that follow dedicated oligomerization path

SUBMITTER: Van der Rest G 

PROVIDER: S-EPMC6704068 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature