Structural and dynamic properties of the human prion protein.

ABSTRACT: Prion diseases involve the conformational conversion of the cellular prion protein (PrP(C)) to its misfolded pathogenic form (PrP(Sc)). To better understand the structural mechanism of this conversion, we performed extensive all-atom, explicit-solvent molecular-dynamics simulations for three structures of the wild-type human PrP (huPrP) at different pH values and temperatures. Residue 129 is polymorphic, being either Met or Val. Two of the three structures have Met in position 129 and the other has Val. Lowering the pH or raising the temperature induced large conformational changes of the C-terminal globular domain and increased exposure of its hydrophobic core. In some simulations, HA and its preceding S1-HA loop underwent large displacements. The C-terminus of HB was unstable and sometim

SUBMITTER: Chen W 

PROVIDER: S-EPMC4026773 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature