The landscape of the prion protein's structural response to mutation revealed by principal component analysis of multiple NMR ensembles.

ABSTRACT: Prion Proteins (PrP) are among a small number of proteins for which large numbers of NMR ensembles have been resolved for sequence mutants and diverse species. Here, we perform a comprehensive principle components analysis (PCA) on the tertiary structures of PrP globular proteins to discern PrP subdomains that exhibit conformational change in response to point mutations and clade-specific evolutionary sequence mutation trends. This is to our knowledge the first such large-scale analysis of multiple NMR ensembles of protein structures, and the first study of its kind for PrPs. We conducted PCA on human (n = 11), mouse (n = 14), and wildtype (n = 21) sets of PrP globular structures, from which we identified five conformationally variable subdomains within PrP. PCA shows that different non-lo

SUBMITTER: Gendoo DM 

PROVIDER: S-EPMC3415401 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature