2a3i

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[[Image:2a3i.gif|left|200px]]
 
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==Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor==
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The line below this paragraph, containing "STRUCTURE_2a3i", creates the "Structure Box" on the page.
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<StructureSection load='2a3i' size='340' side='right'caption='[[2a3i]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2a3i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A3I 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]] 1.95&#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=C0R:CORTICOSTERONE'>C0R</scene></td></tr>
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{{STRUCTURE_2a3i| PDB=2a3i | SCENE= }}
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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=2a3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a3i OCA], [https://pdbe.org/2a3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a3i RCSB], [https://www.ebi.ac.uk/pdbsum/2a3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a3i ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[https://omim.org/entry/177735 177735]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[https://omim.org/entry/605115 605115]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>
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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/a3/2a3i_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=2a3i ConSurf].
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<div style="clear:both"></div>
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'''Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor'''
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==See Also==
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*[[Mineralocorticoid receptor|Mineralocorticoid receptor]]
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== References ==
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==Overview==
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<references/>
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Mineralocorticoid receptor (MR) controls sodium homeostasis and blood pressure through hormone binding and coactivator recruitment. Here, we report a 1.95 A crystal structure of the MR ligand binding domain containing a single C808S mutation bound to corticosterone and the fourth LXXLL motif of steroid receptor coactivator-1 (SRC1-4). Through a combination of biochemical and structural analyses, we demonstrate that SRC1-4 is the most potent MR binding motif and mutations that disrupt the MR/SRC1-4 interactions abolish the ability of the full-length SRC1 to coactivate MR. The structure also reveals a compact steroid binding pocket with a unique topology that is primarily defined by key residues of helices 6 and 7. Mutations swapping a single residue at position 848 from helix H7 between MR and glucocorticoid receptor (GR) switch their hormone specificity. Together, these findings provide critical insights into the molecular basis of hormone binding and coactivator recognition by MR and related steroid receptors.
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__TOC__
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</StructureSection>
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==About this Structure==
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2A3I is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A3I OCA].
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==Reference==
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Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor., Li Y, Suino K, Daugherty J, Xu HE, Mol Cell. 2005 Aug 5;19(3):367-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16061183 16061183]
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[[Category: Histone acetyltransferase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Daugherty, J.]]
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[[Category: Daugherty J]]
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[[Category: Li, Y.]]
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[[Category: Li Y]]
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[[Category: Suino, K.]]
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[[Category: Suino K]]
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[[Category: Xu, H E.]]
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[[Category: Xu HE]]
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[[Category: Transcription factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:33:15 2008''
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Current revision

Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor

PDB ID 2a3i

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