5b41
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of VDR-LBD complexed with 2-methylidene-19-nor-1a,25-dihydroxyvitamin D3== | |
| + | <StructureSection load='5b41' size='340' side='right' caption='[[5b41]], [[Resolution|resolution]] 1.89Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5b41]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B41 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YSV:(1R,3R)-5-(2-((1R,3AS,7AR,E)-1-((R)-6-HYDROXY-6-METHYLHEPTAN-2-YL)-7A-METHYLOCTAHYDRO-4H-INDEN-4-YLIDENE)ETHYLIDENE)-2-METHYLENECYCLOHEXANE-1,3-DIOL'>YSV</scene></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=5b41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b41 OCA], [http://pdbe.org/5b41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b41 RCSB], [http://www.ebi.ac.uk/pdbsum/5b41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b41 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/VDR_RAT VDR_RAT]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:17227670</ref> [[http://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Vitamin D receptor (VDR) controls the expression of numerous genes through the conformational change caused by binding 1alpha,25-dihydroxyvitamin D3. Helix 12 in the ligand-binding domain (LBD) is key to regulating VDR activation. The structures of apo VDR-LBD and the VDR-LBD/antagonist complex are unclear. Here, we reveal their unprecedented structures in solution using a hybrid method combining small-angle X-ray scattering and molecular dynamics simulations. In apo rat VDR-LBD, helix 12 is partially unraveled, and it is positioned around the canonical active position and fluctuates. Helix 11 greatly bends toward the outside at Q396, creating a kink. In the rat VDR-LBD/antagonist complex, helix 12 does not generate the activation function 2 surface, and loop 11-12 is remarkably flexible compared to that in the apo rat VDR-LBD. On the basis of these structural insights, we propose a "folding-door model" to describe the mechanism of agonism/antagonism of VDR-LBD. | ||
| - | + | Apo- and Antagonist-Binding Structures of Vitamin D Receptor Ligand-Binding Domain Revealed by Hybrid Approach Combining Small-Angle X-ray Scattering and Molecular Dynamics.,Anami Y, Shimizu N, Ekimoto T, Egawa D, Itoh T, Ikeguchi M, Yamamoto K J Med Chem. 2016 Sep 8;59(17):7888-900. doi: 10.1021/acs.jmedchem.6b00682. Epub, 2016 Aug 26. PMID:27535484<ref>PMID:27535484</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5b41" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Anami, Y]] | [[Category: Anami, Y]] | ||
[[Category: Itoh, T]] | [[Category: Itoh, T]] | ||
| + | [[Category: Yamamoto, K]] | ||
| + | [[Category: Co-factor]] | ||
| + | [[Category: Rxr]] | ||
| + | [[Category: Transcription]] | ||
| + | [[Category: Vdr]] | ||
| + | [[Category: Vdre]] | ||
| + | [[Category: Vitamin d3]] | ||
Revision as of 19:37, 9 December 2016
Crystal structure of VDR-LBD complexed with 2-methylidene-19-nor-1a,25-dihydroxyvitamin D3
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Categories: Anami, Y | Itoh, T | Yamamoto, K | Co-factor | Rxr | Transcription | Vdr | Vdre | Vitamin d3
