1ya3

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{{STRUCTURE_1ya3| PDB=1ya3 | SCENE= }}
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==Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to progesterone and harboring the S810L mutation responsible for a severe form of hypertension==
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===Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to progesterone and harboring the S810L mutation responsible for a severe form of hypertension===
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<StructureSection load='1ya3' size='340' side='right' caption='[[1ya3]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
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{{ABSTRACT_PUBMED_15908963}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ya3]] is a 3 chain structure with sequence 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=1YA3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YA3 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=STR:PROGESTERONE'>STR</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ya3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ya3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ya3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ya3 PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://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:[http://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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[[http://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/ya/1ya3_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/chain_selection.php?pdb_ID=2ata 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 S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension and switches progesterone from antagonist to agonist. Here we report the crystal structures of the ligand-binding domain of MR S810L in complex with progesterone and deoxycorticosterone, an agonist of both wild-type and mutant MRs. These structures, the first for MR, identify the specific contacts created by Leu810 and clarify the mechanism of activation of MR S810L.
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==Disease==
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Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.,Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin ME Nat Struct Mol Biol. 2005 Jun;12(6):554-5. Epub 2005 May 22. PMID:15908963<ref>PMID:15908963</ref>
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[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://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:[http://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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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://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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</div>
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== References ==
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==About this Structure==
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<references/>
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[[1ya3]] is a 3 chain structure with sequence 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=1YA3 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:015908963</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Fagart, J.]]
[[Category: Fagart, J.]]

Revision as of 20:49, 29 September 2014

Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to progesterone and harboring the S810L mutation responsible for a severe form of hypertension

1ya3, resolution 2.34Å

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