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5va0
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Glucocorticoid Receptor DNA Binding Domain in complex with AP-1 response element from VCAM-1 Promoter== | |
| + | <StructureSection load='5va0' size='340' side='right' caption='[[5va0]], [[Resolution|resolution]] 2.29Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5va0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VA0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VA0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5va7|5va7]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5va0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5va0 OCA], [http://pdbe.org/5va0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5va0 RCSB], [http://www.ebi.ac.uk/pdbsum/5va0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5va0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[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> | ||
| + | == Function == | ||
| + | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that controls the expression of extensive gene networks, driving both up- and down-regulation. GR utilizes multiple DNA-binding-dependent and -independent mechanisms to achieve context-specific transcriptional outcomes. The DNA-binding-independent mechanism involves tethering of GR to the pro-inflammatory transcription factor activator protein-1 (AP-1) through protein-protein interactions. This mechanism has served as the predominant model of GR-mediated transrepression of inflammatory genes. However, ChIP-seq data have consistently shown GR to occupy AP-1 response elements (TREs), even in the absence of AP-1. Therefore, the current model is insufficient to explain GR action at these sites. Here, we show that GR regulates a subset of inflammatory genes in a DNA-binding-dependent manner. Using structural biology and biochemical approaches, we show that GR binds directly to TREs via sequence-specific contacts to a GR-binding sequence (GBS) half-site found embedded within the TRE motif. Furthermore, we show that GR-mediated transrepression observed at TRE sites to be DNA-binding-dependent. This represents a paradigm shift in the field, showing that GR uses multiple mechanisms to suppress inflammatory gene expression. This work further expands our understanding of this complex multifaceted transcription factor. | ||
| - | + | Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes.,Weikum ER, de Vera IMS, Nwachukwu JC, Hudson WH, Nettles KW, Kojetin DJ, Ortlund EA Nucleic Acids Res. 2017 Jun 7. doi: 10.1093/nar/gkx509. PMID:28591827<ref>PMID:28591827</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Weikum, E | + | <div class="pdbe-citations 5va0" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Ortlund, E A]] | ||
| + | [[Category: Weikum, E R]] | ||
| + | [[Category: Development]] | ||
| + | [[Category: Dna binding]] | ||
| + | [[Category: Nuclear receptor]] | ||
| + | [[Category: Protein-dna complex]] | ||
| + | [[Category: Transcription factor]] | ||
| + | [[Category: Transcription-dna complex]] | ||
Revision as of 06:02, 17 August 2017
Glucocorticoid Receptor DNA Binding Domain in complex with AP-1 response element from VCAM-1 Promoter
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