2Q1H
Ancestral Corticoid Receptor in Complex with Aldosterone
Summary for 2Q1H
| Entry DOI | 10.2210/pdb2q1h/pdb |
| Descriptor | AncCR, SODIUM ION, ALDOSTERONE, ... (5 entities in total) |
| Functional Keywords | nuclear receptor, ligand binding domain, aldosterone, evolution, ancient protein, epistasis, unknown function, transcription |
| Biological source | unidentified |
| Total number of polymer chains | 1 |
| Total formula weight | 29643.32 |
| Authors | Ortlund, E.A.,Bridgham, J.T.,Redinbo, M.R.,Thornton, J.W. (deposition date: 2007-05-24, release date: 2007-09-04, Last modification date: 2024-01-31) |
| Primary citation | Ortlund, E.A.,Bridgham, J.T.,Redinbo, M.R.,Thornton, J.W. Crystal structure of an ancient protein: evolution by conformational epistasis. Science, 317:1544-1548, 2007 Cited by PubMed Abstract: 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 approximately 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. PubMed: 17702911DOI: 10.1126/science.1142819 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
