Methionine sulfoxides on prion protein Helix-3 switch on the alpha-fold destabilization required for conversion.

ABSTRACT:

Background

The conversion of the cellular prion protein (PrP(C)) into the infectious form (PrP(Sc)) is the key event in prion induced neurodegenerations. This process is believed to involve a multi-step conformational transition from an alpha-helical (PrP(C)) form to a beta-sheet-rich (PrP(Sc)) state. In addition to the conformational difference, PrP(Sc) exhibits as covalent signature the sulfoxidation of M213. To investigate whether such modification may play a role in the misfolding process we have studied the impact of methionine oxidation on the dynamics and energetics of the HuPrP(125-229) alpha-fold.

Methodology/principal findings

Using molecular dynamics simulation, essential dynamics, correlated motions and signal propagation analysis, we have found that substitution

SUBMITTER: Colombo G 

PROVIDER: S-EPMC2628723 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature