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| | <StructureSection load='5x8s' size='340' side='right'caption='[[5x8s]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='5x8s' size='340' side='right'caption='[[5x8s]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x8s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hylobates_concolor_leucogenys Hylobates concolor leucogenys]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X8S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5X8S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x8s]] is a 2 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=5X8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X8S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Q5:Ursolic+acid'>6Q5</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x8x|5x8x]], [[5x8u|5x8u]], [[5x8w|5x8w]], [[5x8q|5x8q]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Q5:Ursolic+acid'>6Q5</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RORC, NR1F3, RORG, RZRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=61853 Hylobates concolor leucogenys])</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=5x8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x8s OCA], [https://pdbe.org/5x8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x8s RCSB], [https://www.ebi.ac.uk/pdbsum/5x8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x8s 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=5x8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x8s OCA], [http://pdbe.org/5x8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x8s RCSB], [http://www.ebi.ac.uk/pdbsum/5x8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x8s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. | + | [https://www.uniprot.org/uniprot/G1RH57_NOMLE G1RH57_NOMLE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hylobates concolor leucogenys]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Adachi, T]] | + | [[Category: Adachi T]] |
| - | [[Category: Doi, S]] | + | [[Category: Doi S]] |
| - | [[Category: Murase, K]] | + | [[Category: Murase K]] |
| - | [[Category: Noguchi, M]] | + | [[Category: Noguchi M]] |
| - | [[Category: Nomura, A]] | + | [[Category: Nomura A]] |
| - | [[Category: Yamaguchi, K]] | + | [[Category: Yamaguchi K]] |
| - | [[Category: Binary complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Nuclear receptor]]
| + | |
| - | [[Category: Transferase-inhibitor complex]]
| + | |
| Structural highlights
Function
G1RH57_NOMLE
Publication Abstract from PubMed
Retinoid-related orphan receptor gamma (RORgamma) directly controls the differentiation of Th17 cell and the production of interleukin-17, which plays an integral role in autoimmune diseases. To obtain insight into RORgamma, we have determined the first crystal structure of a ternary complex containing RORgamma ligand-binding domain (LBD) bound with a novel synthetic inhibitor and a repressor peptide, 22-mer peptide from silencing mediator of retinoic acid and thyroid hormone receptor (SMRT). Comparison of a binary complex of nonliganded (apo) RORgamma-LBD with a nuclear receptor co-activator (NCoA-1) peptide has shown that our inhibitor displays a unique mechanism different from those caused by natural inhibitor, ursolic acid (UA). The compound unprecedentedly induces indirect disruption of a hydrogen bond between His479 on helix 11 (H11) and Tyr502 on H12, which is crucial for active conformation. This crystallographic study will allow us to develop novel synthetic compounds for autoimmune disease therapy.
Ternary complex of human RORgamma ligand-binding domain, inverse agonist and SMRT peptide shows a unique mechanism of corepressor recruitment.,Noguchi M, Nomura A, Murase K, Doi S, Yamaguchi K, Hirata K, Shiozaki M, Hirashima S, Kotoku M, Yamaguchi T, Katsuda Y, Steensma R, Li X, Tao H, Tse B, Fenn M, Babine R, Bradley E, Crowe P, Thacher S, Adachi T, Kamada M Genes Cells. 2017 Jun;22(6):535-551. doi: 10.1111/gtc.12494. Epub 2017 May 11. PMID:28493531[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Noguchi M, Nomura A, Murase K, Doi S, Yamaguchi K, Hirata K, Shiozaki M, Hirashima S, Kotoku M, Yamaguchi T, Katsuda Y, Steensma R, Li X, Tao H, Tse B, Fenn M, Babine R, Bradley E, Crowe P, Thacher S, Adachi T, Kamada M. Ternary complex of human RORgamma ligand-binding domain, inverse agonist and SMRT peptide shows a unique mechanism of corepressor recruitment. Genes Cells. 2017 Jun;22(6):535-551. doi: 10.1111/gtc.12494. Epub 2017 May 11. PMID:28493531 doi:http://dx.doi.org/10.1111/gtc.12494
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