View source for 6cfn


==Crystal Structure of the DNA-free Glucocorticoid Receptor DNA Binding Domain==
<StructureSection load='6cfn' size='340' side='right'caption='[[6cfn]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cfn]] is a 8 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=6CFN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CFN FirstGlance]. <br>
</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>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cfn OCA], [https://pdbe.org/6cfn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cfn RCSB], [https://www.ebi.ac.uk/pdbsum/6cfn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cfn ProSAT]</span></td></tr>
</table>
== 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> 
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== Publication Abstract from PubMed ==
The glucocorticoid receptor (GR) is a steroid hormone receptor of the nuclear receptor family that regulates gene expression in response to glucocorticoid hormone signaling. Interaction with specific GR DNA binding sequences causes conformational changes in the GR DNA binding domain (DBD) that result in recruitment of specific sets of co-regulators that determine transcriptional outcomes. We have solved the crystal structure of GR DBD in its DNA-free state, the first such crystal structure from any nuclear receptor. In contrast to previous NMR structures, this crystal structure reveals that free GR DBD adopts a conformation very similar to DNA-bound states. The lever arm region is the most variable element in the free GR DBD. Molecular dynamics of the free GR DBD as well as GR DBD bound to activating and repressive DNA elements confirm lever arm flexibility in all functional states. Cluster analysis of lever arm conformations during simulations shows that DNA binding and dimerization cause a reduction in the number of conformations sampled by the lever arm. These results reveal that DNA binding and dimerization drive conformational selection in the GR DBD lever arm region and show how DNA allosterically controls GR structure and dynamics.

The first crystal structure of a DNA-free nuclear receptor DNA binding domain sheds light on DNA-driven allostery in the glucocorticoid receptor.,Frank F, Okafor CD, Ortlund EA Sci Rep. 2018 Sep 10;8(1):13497. doi: 10.1038/s41598-018-31812-9. PMID:30201977<ref>PMID:30201977</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6cfn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Frank F]]
[[Category: Okafor CD]]
[[Category: Ortlund EA]]