Disease-associated mutations disrupt functionally important regions of intrinsic protein disorder.

ABSTRACT: The effects of disease mutations on protein structure and function have been extensively investigated, and many predictors of the functional impact of single amino acid substitutions are publicly available. The majority of these predictors are based on protein structure and evolutionary conservation, following the assumption that disease mutations predominantly affect folded and conserved protein regions. However, the prevalence of the intrinsically disordered proteins (IDPs) and regions (IDRs) in the human proteome together with their lack of fixed structure and low sequence conservation raise a question about the impact of disease mutations in IDRs. Here, we investigate annotated missense disease mutations and show that 21.7% of them are located within such intrinsically disordered regio

SUBMITTER: Vacic V 

PROVIDER: S-EPMC3464192 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature