2q3y
From Proteopedia
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Ancestral Corticiod Receptor in Complex with DOC
Contents |
Overview
The structural mechanisms by which proteins have evolved new functions are, known only indirectly. We report x-ray crystal structures of a resurrected, ancestral protein-the ~450 million-year-old precursor of vertebrate, glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using, structural, phylogenetic, and functional analysis, we identify the, specific set of historical mutations that recapitulate the evolution of, GR's hormone specificity from an MR-like ancestor. These substitutions, repositioned crucial residues to create new receptor-ligand and, intraprotein contacts. Strong epistatic interactions occur because one, substitution changes the conformational position of another site., "Permissive" mutations-substitutions of no immediate consequence, which, stabilize specific elements of the protein and allow it to tolerate, subsequent function-switching changes-played a major role in determining, GR's evolutionary trajectory.
Disease
Known diseases associated with this structure: Obesity, mild, early-onset OMIM:[604630]
About this Structure
2Q3Y is a Single protein structure of sequence from Unidentified with 1CA and GOL as ligands. Full crystallographic information is available from OCA.
Reference
Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis., Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW, Science. 2007 Aug 16;. PMID:17702911
Page seeded by OCA on Mon Nov 12 23:29:22 2007
