Protein Structure

Functional Evolution of Proteins

Science's STKE  18 Sep 2007:
Vol. 2007, Issue 404, pp. tw340
DOI: 10.1126/stke.4042007tw340

The direct identification of protein evolution mechanisms requires comparing proteins through evolutionary time. The sequence of the 450-million-year-old ancestor of vertebrate mineralocorticoid (MR) and glucocorticoid (GR) receptors was previously determined by phylogenetic analysis, and the ancestor was shown to have MR-like hormone specificity. Ortlund et al. used structural, functional, and phylogenetic analysis to determine how specific mutations resulted in a change from MR-like to GR hormone specificity. They find evidence for epistatic interactions where a substitution changed the conformation at another site. Substitutions that had no immediate functional effect, but affected stability to allow subsequent function-switching mutations, played an important role in GR evolution.

E. A. Ortlund, J. T. Bridgham, M. R. Redinbo, J. W. Thornton, Crystal structure of an ancient protein: Evolution by conformational epistasis. Science 317, 1544-1548 (2007). [Abstract] [Full Text]