View source for 9hdf


==Glucocorticoid Receptor Ligand Binding Domain in complex with dexamethasone==
<StructureSection load='9hdf' size='340' side='right'caption='[[9hdf]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hdf]] is a 32 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=9HDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HDF 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]] 2.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=DEX:DEXAMETHASONE'>DEX</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9hdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hdf OCA], [https://pdbe.org/9hdf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hdf RCSB], [https://www.ebi.ac.uk/pdbsum/9hdf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hdf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:11136233</ref> 
== Function ==
[https://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.<ref>PMID:14752053</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The glucocorticoid receptor (GR) is a leading drug target due to its antiinflammatory and immunosuppressive roles. The functional oligomeric conformation of full-length GR (FL-GR), which is key for its biological activity, remains disputed. Here we present a new crystal structure of agonist-bound GR ligand-binding domain (GR-LBD) comprising eight copies of a noncanonical dimer. We verified the biological relevance of this dimer for receptor multimerization in wild-type and selected FL-GR mutants using molecular dynamics and crosslinking-mass spectrometry together with fluorescence microscopy and transcriptomic analysis in living cells. Self-association of this GR-LBD basic dimer in two mutually exclusive assemblies reveals clues for FL-GR multimerization and activity in cells. We propose a model for the structure of multidomain GR based on our new data and suggest a detailed oligomerization pathway. This model reconciles all currently available structural and functional information and provides a more comprehensive understanding of the rare disorder, generalized glucocorticoid resistance.

The multimerization pathway of the glucocorticoid receptor.,Alegre-Marti A, Jimenez-Panizo A, Lafuente AL, Johnson TA, Montoya-Novoa I, Peralta-Moreno MN, Montanya-Valluguera P, Ponseti-Pons J, Abella M, Kim S, Diaz M, Vilaseca M, Perez P, Fernandez-Recio J, Rubio-Martinez J, Presman DM, Hager GL, Fuentes-Prior P, Estebanez-Perpina E Nucleic Acids Res. 2025 Oct 14;53(19):gkaf1003. doi: 10.1093/nar/gkaf1003. PMID:41118578<ref>PMID:41118578</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hdf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alegre-Marti A]]
[[Category: Estebanez-Perpina E]]
[[Category: Fuentes-Prior P]]
[[Category: Jimenez-Panizo A]]