Evolutionary Divergent Suppressor Mutations in Conformational Diseases.

ABSTRACT: Neutral and adaptive mutations are key players in the evolutionary dynamics of proteins at molecular, cellular and organismal levels. Conversely, largely destabilizing mutations are rarely tolerated by evolution, although their occurrence in diverse human populations has important roles in the pathogenesis of conformational diseases. We have recently proposed that divergence at certain sites from the consensus (amino acid) state during mammalian evolution may have rendered some human proteins more vulnerable towards disease-associated mutations, primarily by decreasing their conformational stability. We herein extend and refine this hypothesis discussing results from phylogenetic and structural analyses, structure-based energy calculations and structure-function studies at molecular and ce

SUBMITTER: Mesa-Torres N 

PROVIDER: S-EPMC6071075 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature