2q1v
From Proteopedia
(New page: 200px<br /><applet load="2q1v" size="350" color="white" frame="true" align="right" spinBox="true" caption="2q1v, resolution 1.95Å" /> '''Ancestral corticoid ...) |
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==Overview== | ==Overview== | ||
| - | The structural mechanisms by which proteins have evolved new functions are | + | 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Crystal | + | Crystal structure of an ancient protein: evolution by conformational epistasis., Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW, Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17702911 17702911] |
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Unidentified]] | [[Category: Unidentified]] | ||
| - | [[Category: Ortlund, E | + | [[Category: Ortlund, E A.]] |
| - | [[Category: Redinbo, M | + | [[Category: Redinbo, M R.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: PDN]] | [[Category: PDN]] | ||
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[[Category: transcription]] | [[Category: transcription]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:35:10 2008'' |
Revision as of 16:35, 21 February 2008
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Ancestral corticoid receptor in complex with cortisol
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 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.
About this Structure
2Q1V is a Protein complex structure of sequences from Unidentified with and 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 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:17702911
Page seeded by OCA on Thu Feb 21 18:35:10 2008
