1m2z: Difference between revisions

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-[[Image:1m2z.gif|left|200px]]
- {{Structure
+==Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif==
-|PDB= 1m2z |SIZE=350|CAPTION= <scene name='initialview01'>1m2z</scene>, resolution 2.50&Aring;
+<StructureSection load='1m2z' size='340' side='right'caption='[[1m2z]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DEX:DEXAMETHASONE'>DEX</scene>
+<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>
-|ACTIVITY=
+</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>
-|GENE=
+<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>
-|DOMAIN=
+<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>
-|RELATEDENTRY=
+</table>
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m2z OCA], [http://www.ebi.ac.uk/pdbsum/1m2z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1m2z RCSB]</span>
+== Disease ==
-}}
+[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>
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m2/1m2z_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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].
+<div style="clear:both"></div>
-'''Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif'''
+==See Also==
+*[[Glucocorticoid receptor|Glucocorticoid receptor]]
+*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
-==Overview==
+== References ==
-Transcriptional regulation by the glucocorticoid receptor (GR) is mediated by hormone binding, receptor dimerization, and coactivator recruitment. Here, we report the crystal structure of the human GR ligand binding domain (LBD) bound to dexamethasone and a coactivator motif derived from the transcriptional intermediary factor 2. Despite structural similarity to other steroid receptors, the GR LBD adopts a surprising dimer configuration involving formation of an intermolecular beta sheet. Functional studies demonstrate that the novel dimer interface is important for GR-mediated activation. The structure also reveals an additional charge clamp that determines the binding selectivity of a coactivator and a distinct ligand binding pocket that explains its selectivity for endogenous steroid hormones. These results establish a framework for understanding the roles of protein-hormone and protein-protein interactions in GR signaling pathways.
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-M2Z 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=1M2Z OCA].
-==Reference==
-Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition., Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE, Cell. 2002 Jul 12;110(1):93-105. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12151000 12151000]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Apolito, C J.]]
+[[Category: Apolito CJ]]
-[[Category: Bledsoe, R B.]]
+[[Category: Bledsoe RB]]
-[[Category: Consler, T G.]]
+[[Category: Consler TG]]
-[[Category: Delves, C J.]]
+[[Category: Delves CJ]]
-[[Category: Lambert, M H.]]
+[[Category: Lambert MH]]
-[[Category: Mckee, D D.]]
+[[Category: Mckee DD]]
-[[Category: Montana, V G.]]
+[[Category: Montana VG]]
-[[Category: Moore, J T.]]
+[[Category: Moore JT]]
-[[Category: Parks, D J.]]
+[[Category: Parks DJ]]
-[[Category: Pearce, K H.]]
+[[Category: Pearce KH]]
-[[Category: Stanley, T B.]]
+[[Category: Stanley TB]]
-[[Category: Stewart, E L.]]
+[[Category: Stewart EL]]
-[[Category: Willson, T M.]]
+[[Category: Willson TM]]
-[[Category: Xu, H E.]]
+[[Category: Xu HE]]
-[[Category: charge clamp]]
-[[Category: coactivator]]
-[[Category: dexamethasone]]
-[[Category: dimer interface]]
-[[Category: glucocorticoid receptor]]
-[[Category: hormone binding pocket]]
-[[Category: tif2]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:10:35 2008''