The Contribution of Missense Mutations in Core and Rim Residues of Protein-Protein Interfaces to Human Disease.

ABSTRACT: Missense mutations at protein-protein interaction sites, called interfaces, are important contributors to human disease. Interfaces are non-uniform surface areas characterized by two main regions, "core" and "rim", which differ in terms of evolutionary conservation and physicochemical properties. Moreover, within interfaces, only a small subset of residues ("hot spots") is crucial for the binding free energy of the protein-protein complex. We performed a large-scale structural analysis of human single amino acid variations (SAVs) and demonstrated that disease-causing mutations are preferentially located within the interface core, as opposed to the rim (p<0.01). In contrast, the interface rim is significantly enriched in polymorphisms, similar to the remaining non-interacting surface. Energ

SUBMITTER: David A 

PROVIDER: S-EPMC4548493 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature