1a52

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[[Image:1a52.gif|left|200px]]<br /><applet load="1a52" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1a52, resolution 2.8&Aring;" />
 
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'''ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN COMPLEXED TO ESTRADIOL'''<br />
 
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==Overview==
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==ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN COMPLEXED TO ESTRADIOL==
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The 2.8-A crystal structure of the complex formed by estradiol and the human estrogen receptor-alpha ligand binding domain (hERalphaLBD) is described and compared with the recently reported structure of the progesterone complex of the human progesterone receptor ligand binding domain, as well as with similar structures of steroid/nuclear receptor LBDs solved elsewhere. The hormone-bound hERalphaLBD forms a distinctly different and probably more physiologically important dimer interface than its progesterone counterpart. A comparison of the specificity determinants of hormone binding reveals a common structural theme of mutually supported van der Waals and hydrogen-bonded interactions involving highly conserved residues. The previously suggested mechanism by which the estrogen receptor distinguishes estradiol's unique 3-hydroxy group from the 3-keto function of most other steroids is now described in atomic detail. Mapping of mutagenesis results points to a coactivator-binding surface that includes the region around the "signature sequence" as well as helix 12, where the ligand-dependent conformation of the activation function 2 core is similar in all previously solved steroid/nuclear receptor LBDs. A peculiar crystal packing event displaces helix 12 in the hERalphaLBD reported here, suggesting a higher degree of dynamic variability than expected for this critical substructure.
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<StructureSection load='1a52' size='340' side='right'caption='[[1a52]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1a52]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The September 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Estrogen Receptor'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_9 10.2210/rcsb_pdb/mom_2003_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A52 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A52 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]] 2.8&#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=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=EST:ESTRADIOL'>EST</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=1a52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a52 OCA], [https://pdbe.org/1a52 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a52 RCSB], [https://www.ebi.ac.uk/pdbsum/1a52 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a52 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</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/a5/1a52_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=1a52 ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]]
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*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1A52 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=EST:'>EST</scene> and <scene name='pdbligand=AU:'>AU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 1A52 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb45_1.html Estrogen Receptor]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A52 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains., Tanenbaum DM, Wang Y, Williams SP, Sigler PB, Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9600906 9600906]
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[[Category: Estrogen Receptor]]
[[Category: Estrogen Receptor]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Sigler, P B.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Tanenbaum, D M.]]
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[[Category: Sigler PB]]
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[[Category: Wang, Y.]]
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[[Category: Tanenbaum DM]]
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[[Category: AU]]
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[[Category: Wang Y]]
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[[Category: EST]]
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[[Category: estrogen]]
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[[Category: ligand]]
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[[Category: receptor]]
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[[Category: transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:40:55 2008''
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Current revision

ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN COMPLEXED TO ESTRADIOL

PDB ID 1a52

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