2q3y
From Proteopedia
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|PDB= 2q3y |SIZE=350|CAPTION= <scene name='initialview01'>2q3y</scene>, resolution 2.40Å | |PDB= 2q3y |SIZE=350|CAPTION= <scene name='initialview01'>2q3y</scene>, resolution 2.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=1CA:DESOXYCORTICOSTERONE'>1CA</scene> | + | |LIGAND= <scene name='pdbligand=1CA:DESOXYCORTICOSTERONE'>1CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2q1v|2Q1V]], [[2q1h|2Q1H]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q3y OCA], [http://www.ebi.ac.uk/pdbsum/2q3y PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q3y RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Obesity, mild, early-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604630 604630]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Redinbo, M R.]] | [[Category: Redinbo, M R.]] | ||
[[Category: Thornton, J W.]] | [[Category: Thornton, J W.]] | ||
| - | [[Category: 1CA]] | ||
| - | [[Category: GOL]] | ||
[[Category: cortisol]] | [[Category: cortisol]] | ||
[[Category: doc]] | [[Category: doc]] | ||
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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 Mon Mar 31 04:44:17 2008'' |
Revision as of 01:44, 31 March 2008
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| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Related: | 2Q1V, 2Q1H
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Ancestral Corticiod Receptor in Complex with DOC
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
2Q3Y is a Single protein structure of sequence from Unidentified. 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 Mon Mar 31 04:44:17 2008
