Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors.

ABSTRACT: The genetic and biophysical mechanisms by which new protein functions evolve is a central question in evolutionary biology, biochemistry, and biophysics. Of particular interest is whether major shifts in protein function are caused by a few mutations of large effect and, if they are, the mechanisms that mediate these changes. Here we combine ancestral protein reconstruction with genetic manipulation and explicit studies of protein structure and dynamics to dissect an ancient and discrete shift in ligand specificity in the steroid receptors, a family of biologically essential hormone-controlled transcription factors. We previously found that the ancestor of the entire steroid receptor family was highly specific for estrogens, but its immediate phylogenetic descendant was sensitive only to a

SUBMITTER: Harms MJ 

PROVIDER: S-EPMC3710831 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature