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| | <StructureSection load='1vjb' size='340' side='right'caption='[[1vjb]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='1vjb' size='340' side='right'caption='[[1vjb]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1vjb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VJB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1VJB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1vjb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VJB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OHT:4-HYDROXYTAMOXIFEN'>OHT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kv6|1kv6]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OHT:4-HYDROXYTAMOXIFEN'>OHT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Esrrg, Err3, Kiaa0832, Nr3b3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1vjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vjb OCA], [https://pdbe.org/1vjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vjb RCSB], [https://www.ebi.ac.uk/pdbsum/1vjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vjb ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1vjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vjb OCA], [http://pdbe.org/1vjb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vjb RCSB], [http://www.ebi.ac.uk/pdbsum/1vjb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1vjb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ERR3_MOUSE ERR3_MOUSE]] Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements.<ref>PMID:10428842</ref> | + | [https://www.uniprot.org/uniprot/ERR3_HUMAN ERR3_HUMAN] Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).<ref>PMID:19067653</ref> <ref>PMID:18063693</ref> <ref>PMID:11864604</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Flaig, R]] | + | [[Category: Flaig R]] |
| - | [[Category: Greschik, H]] | + | [[Category: Greschik H]] |
| - | [[Category: Moras, D]] | + | [[Category: Moras D]] |
| - | [[Category: Renaud, J P]] | + | [[Category: Renaud JP]] |
| - | [[Category: Antagonist complex]]
| + | |
| - | [[Category: Ligand-binding domain]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
ERR3_HUMAN Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The estrogen-related receptor (ERR) gamma behaves as a constitutive activator of transcription. Although no natural ligand is known, ERRgamma is deactivated by the estrogen receptor (ER) agonist diethylstilbestrol and the selective ER modulator 4-hydroxytamoxifen but does not significantly respond to estradiol or raloxifene. Here we report the crystal structures of the ERRgamma ligand binding domain (LBD) complexed with diethylstilbestrol or 4-hydroxytamoxifen. Antagonist binding to ERRgamma results in a rotation of the side chain of Phe-435 that partially fills the cavity of the apoLBD. The new rotamer of Phe-435 displaces the "activation helix" (helix 12) from the agonist position observed in the absence of ligand. In contrast to the complexes of the ERalpha LBD with 4-hydroxytamoxifen or raloxifene, helix 12 of antagonist-bound ERRgamma does not occupy the coactivator groove but appears to be completely dissociated from the LBD body. Comparison of the ligand-bound LBDs of ERRgamma and ERalpha reveals small but significant differences in the architecture of the ligand binding pockets that result in a slightly shifted binding position of diethylstilbestrol and a small rotation of 4-hydroxytamoxifen in the cavity of ERRgamma relative to ERalpha. Our results provide detailed molecular insight into the conformational changes occurring upon binding of synthetic antagonists to the constitutive orphan receptor ERRgamma and reveal structural differences with ERs that explain why ERRgamma does not bind estradiol or raloxifene and will help to design new selective antagonists.
Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity.,Greschik H, Flaig R, Renaud JP, Moras D J Biol Chem. 2004 Aug 6;279(32):33639-46. Epub 2004 May 24. PMID:15161930[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hentschke M, Susens U, Borgmeyer U. Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases. Biochem J. 2009 Apr 1;419(1):167-76. doi: 10.1042/BJ20081556. PMID:19067653 doi:10.1042/BJ20081556
- ↑ Tremblay AM, Wilson BJ, Yang XJ, Giguere V. Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Mol Endocrinol. 2008 Mar;22(3):570-84. Epub 2007 Dec 6. PMID:18063693 doi:me.2007-0357
- ↑ Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP. Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell. 2002 Feb;9(2):303-13. PMID:11864604
- ↑ Greschik H, Flaig R, Renaud JP, Moras D. Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity. J Biol Chem. 2004 Aug 6;279(32):33639-46. Epub 2004 May 24. PMID:15161930 doi:http://dx.doi.org/10.1074/jbc.M402195200
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