2q1h

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(New page: 200px<br /><applet load="2q1h" size="350" color="white" frame="true" align="right" spinBox="true" caption="2q1h, resolution 1.90&Aring;" /> '''Ancestral Corticoid ...)
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[[Image:2q1h.jpg|left|200px]]<br /><applet load="2q1h" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2q1h, resolution 1.90&Aring;" />
 
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'''Ancestral Corticoid Receptor in Complex with Aldosterone'''<br />
 
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==Overview==
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==Ancestral Corticoid Receptor in Complex with Aldosterone==
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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 ~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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<StructureSection load='2q1h' size='340' side='right'caption='[[2q1h]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2q1h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q1H FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1h OCA], [https://pdbe.org/2q1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q1h RCSB], [https://www.ebi.ac.uk/pdbsum/2q1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q1h ProSAT]</span></td></tr>
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</table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q1/2q1h_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2q1h ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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==About this Structure==
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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<ref>PMID:17702911</ref>
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2Q1H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Unidentified Unidentified] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=AS4:'>AS4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1H OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis., Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW, Science. 2007 Aug 16;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17702911 17702911]
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</div>
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[[Category: Protein complex]]
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<div class="pdbe-citations 2q1h" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Unidentified]]
[[Category: Unidentified]]
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[[Category: Bridgham, J.T.]]
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[[Category: Bridgham JT]]
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[[Category: Ortlund, E.A.]]
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[[Category: Ortlund EA]]
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[[Category: Redinbo, M.R.]]
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[[Category: Redinbo MR]]
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[[Category: Thornton, J.W.]]
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[[Category: Thornton JW]]
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[[Category: AS4]]
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[[Category: GOL]]
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[[Category: NA]]
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[[Category: aldosterone]]
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[[Category: ancient protein]]
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[[Category: epistasis]]
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[[Category: evolution]]
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[[Category: ligand binding domain]]
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[[Category: nuclear receptor]]
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[[Category: transcription]]
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[[Category: unknown function]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:57:23 2008''
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Ancestral Corticoid Receptor in Complex with Aldosterone

PDB ID 2q1h

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