Decrypting Prion Protein Conversion into a β-Rich Conformer by Molecular Dynamics.

ABSTRACT: Prion diseases are fatal neurodegenerative diseases characterized by the formation of β-rich oligomers and the accumulation of amyloid fibrillar deposits in the central nervous system. Understanding the conversion of the cellular prion protein into its β-rich polymeric conformers is fundamental to tackling the early stages of the development of prion diseases. In this paper, we have identified unfolding and refolding steps critical to the conversion into a β-rich conformer for different constructs of the ovine prion protein by molecular dynamics simulations. By combining our results with in vitro experiments, we show that the folded C-terminus of the ovine prion protein is able to recurrently undergo a drastic conformational change by displacement of the H1 helix, uncovering of the

SUBMITTER: Chakroun N 

PROVIDER: S-EPMC3656828 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature