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5b41

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Revision as of 10:03, 26 February 2020

Crystal structure of VDR-LBD complexed with 2-methylidene-19-nor-1a,25-dihydroxyvitamin D3

Structural highlights

5b41 is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Vdr, Nr1i1 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] [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.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

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^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vanhooke JL, Tadi BP, Benning MM, Plum LA, DeLuca HF. New analogs of 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 with conformationally restricted side chains: evaluation of biological activity and structural determination of VDR-bound conformations. Arch Biochem Biophys. 2007 Apr 15;460(2):161-5. Epub 2006 Dec 12. PMID:17227670 doi:10.1016/j.abb.2006.11.029
↑ Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG. The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7939-44. PMID:9653119
↑ Zhang J, Fondell JD. Identification of mouse TRAP100: a transcriptional coregulatory factor for thyroid hormone and vitamin D receptors. Mol Endocrinol. 1999 Jul;13(7):1130-40. PMID:10406464
↑ Wang Q, Sharma D, Ren Y, Fondell JD. A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. J Biol Chem. 2002 Nov 8;277(45):42852-8. Epub 2002 Sep 5. PMID:12218053 doi:10.1074/jbc.M206061200
↑ Ge K, Guermah M, Yuan CX, Ito M, Wallberg AE, Spiegelman BM, Roeder RG. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Nature. 2002 May 30;417(6888):563-7. PMID:12037571 doi:10.1038/417563a
↑ Kang YK, Guermah M, Yuan CX, Roeder RG. The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2642-7. Epub 2002 Feb 26. PMID:11867769 doi:10.1073/pnas.261715899
↑ Coulthard VH, Matsuda S, Heery DM. An extended LXXLL motif sequence determines the nuclear receptor binding specificity of TRAP220. J Biol Chem. 2003 Mar 28;278(13):10942-51. Epub 2003 Jan 29. PMID:12556447 doi:10.1074/jbc.M212950200
↑ Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell. 2003 Nov;12(5):1137-49. PMID:14636573
↑ Wu Q, Burghardt R, Safe S. Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen receptor alpha (ERalpha) involves multiple domains of both proteins. J Biol Chem. 2004 Dec 17;279(51):53602-12. Epub 2004 Oct 5. PMID:15471764 doi:10.1074/jbc.M409778200
↑ Malik S, Guermah M, Yuan CX, Wu W, Yamamura S, Roeder RG. Structural and functional organization of TRAP220, the TRAP/mediator subunit that is targeted by nuclear receptors. Mol Cell Biol. 2004 Sep;24(18):8244-54. PMID:15340084 doi:10.1128/MCB.24.18.8244-8254.2004
↑ Zhang X, Krutchinsky A, Fukuda A, Chen W, Yamamura S, Chait BT, Roeder RG. MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol Cell. 2005 Jul 1;19(1):89-100. PMID:15989967 doi:10.1016/j.molcel.2005.05.015
↑ Udayakumar TS, Belakavadi M, Choi KH, Pandey PK, Fondell JD. Regulation of Aurora-A kinase gene expression via GABP recruitment of TRAP220/MED1. J Biol Chem. 2006 May 26;281(21):14691-9. Epub 2006 Mar 30. PMID:16574658 doi:M600163200
↑ Anami Y, Shimizu N, Ekimoto T, Egawa D, Itoh T, Ikeguchi M, Yamamoto K. 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. J Med Chem. 2016 Sep 8;59(17):7888-900. doi: 10.1021/acs.jmedchem.6b00682. Epub, 2016 Aug 26. PMID:27535484 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00682

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5b41"

@@ Line 1: / Line 1: @@
 ==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]] 1.89&Aring;' scene=''>
+<StructureSection load='5b41' size='340' side='right'caption='[[5b41]], [[Resolution|resolution]] 1.89&Aring;' 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>
+<table><tr><td colspan='2'>[[5b41]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vdr, Nr1i1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5b41" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Vitamin D receptor|Vitamin D receptor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
+[[Category: Large Structures]]
 [[Category: Anami, Y]]
 [[Category: Itoh, T]]

5b41

From Proteopedia

Revision as of 10:03, 26 February 2020

Crystal structure of VDR-LBD complexed with 2-methylidene-19-nor-1a,25-dihydroxyvitamin D3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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