2q1v

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{{STRUCTURE_2q1v| PDB=2q1v | SCENE= }}
{{STRUCTURE_2q1v| PDB=2q1v | SCENE= }}
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'''Ancestral corticoid receptor in complex with cortisol'''
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===Ancestral corticoid receptor in complex with cortisol===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17702911 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17702911}}
==About this Structure==
==About this Structure==
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[[Category: Nuclear receptor]]
[[Category: Nuclear receptor]]
[[Category: Transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:11:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:55:29 2008''

Revision as of 09:55, 29 July 2008

Template:STRUCTURE 2q1v

Ancestral corticoid receptor in complex with cortisol

Template:ABSTRACT PUBMED 17702911

About this Structure

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

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