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1m2z

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{{STRUCTURE_1m2z| PDB=1m2z | SCENE= }}
 
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===Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif===
 
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{{ABSTRACT_PUBMED_12151000}}
 
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==Disease==
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==Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif==
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[[http://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN]] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[http://omim.org/entry/138040 138040]]; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.<ref>PMID:12050230</ref><ref>PMID:1704018</ref><ref>PMID:7683692</ref><ref>PMID:11589680</ref><ref>PMID:11701741</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
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<StructureSection load='1m2z' size='340' side='right'caption='[[1m2z]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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==Function==
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<table><tr><td colspan='2'>[[1m2z]] is a 4 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=1M2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M2Z FirstGlance]. <br>
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[[http://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN]] Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.<ref>PMID:21664385</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
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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]] 2.5&#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=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DEX:DEXAMETHASONE'>DEX</scene></td></tr>
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==About this Structure==
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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=1m2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m2z OCA], [https://pdbe.org/1m2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m2z RCSB], [https://www.ebi.ac.uk/pdbsum/1m2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m2z ProSAT]</span></td></tr>
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[[1m2z]] is a 4 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=1M2Z OCA].
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[https://omim.org/entry/138040 138040]; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.<ref>PMID:12050230</ref> <ref>PMID:1704018</ref> <ref>PMID:7683692</ref> <ref>PMID:11589680</ref> <ref>PMID:11701741</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.<ref>PMID:21664385</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/m2/1m2z_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=1m2z ConSurf].
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<div style="clear:both"></div>
==See Also==
==See Also==
*[[Glucocorticoid receptor|Glucocorticoid receptor]]
*[[Glucocorticoid receptor|Glucocorticoid receptor]]
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*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:012151000</ref><ref group="xtra">PMID:019756040</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Apolito, C J.]]
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[[Category: Large Structures]]
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[[Category: Bledsoe, R B.]]
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[[Category: Apolito CJ]]
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[[Category: Consler, T G.]]
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[[Category: Bledsoe RB]]
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[[Category: Delves, C J.]]
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[[Category: Consler TG]]
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[[Category: Lambert, M H.]]
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[[Category: Delves CJ]]
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[[Category: Mckee, D D.]]
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[[Category: Lambert MH]]
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[[Category: Montana, V G.]]
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[[Category: Mckee DD]]
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[[Category: Moore, J T.]]
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[[Category: Montana VG]]
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[[Category: Parks, D J.]]
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[[Category: Moore JT]]
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[[Category: Pearce, K H.]]
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[[Category: Parks DJ]]
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[[Category: Stanley, T B.]]
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[[Category: Pearce KH]]
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[[Category: Stewart, E L.]]
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[[Category: Stanley TB]]
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[[Category: Willson, T M.]]
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[[Category: Stewart EL]]
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[[Category: Xu, H E.]]
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[[Category: Willson TM]]
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[[Category: Charge clamp]]
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[[Category: Xu HE]]
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[[Category: Coactivator]]
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[[Category: Dexamethasone]]
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[[Category: Dimer interface]]
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[[Category: Glucocorticoid receptor]]
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[[Category: Hormone binding pocket]]
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[[Category: Hormone-hormone activator complex]]
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[[Category: Tif2]]
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Current revision

Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif

PDB ID 1m2z

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