Dynamic diagnosis of familial prion diseases supports the β2-α2 loop as a universal interference target.

ABSTRACT:

Background

Mutations in the cellular prion protein associated to familial prion disorders severely increase the likelihood of its misfolding into pathogenic conformers. Despite their postulation as incompatible elements with the native fold, these mutations rarely modify the native state structure. However they variably have impact on the thermodynamic stability and metabolism of PrP(C) and on the properties of PrP(Sc) aggregates. To investigate whether the pathogenic mutations affect the dynamic properties of the HuPrP(125-229) α-fold and find possible common patterns of effects that could help in prophylaxis we performed a dynamic diagnosis of ten point substitutions.

Methodology/principal findings

Using all-atom molecular dynamics simulations and novel analytical tools we

SUBMITTER: Meli M 

PROVIDER: S-EPMC3084259 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature