Sci. STKE, 18 September 2007
Protein Structure Functional Evolution of Proteins
Valda J. Vinson
Science, AAAS, Washington, DC 20005, USA
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.
Citation: V. J. Vinson, Functional Evolution of Proteins. Sci. STKE 2007, tw340 (2007).
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