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4ruo

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Revision as of 10:17, 1 May 2019

Crystal structure of zVDR L337H mutant-gemini complex

Structural highlights

4ruo is a 2 chain structure with sequence from Brachidanio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2hc4, 2hcd, 4ruj, 4rup
Gene:	vdra, nr1i1a, vdr (Brachidanio rerio)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.

Function

[VDRA_DANRE] 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. Plays a central role in calcium homeostasis.^[1] [NCOA2_HUMAN] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.^[2]

Publication Abstract from PubMed

The bioactive form of vitamin D [1,25(OH)2D3] regulates mineral and bone homeostasis and exerts potent anti-inflammatory and antiproliferative properties through binding to the vitamin D receptor (VDR). The 3D structures of the VDR ligand-binding domain with 1,25(OH)2D3 or gemini analogs unveiled the molecular mechanism underlying ligand recognition. On the basis of structure-function correlations, we generated a point-mutated VDR (VDR(gem)) that is unresponsive to 1,25(OH)2D3, but the activity of which is efficiently induced by the gemini ligands. Moreover, we show that many VDR target genes are repressed by unliganded VDR(gem) and that mineral ion and bone homeostasis are more impaired in VDR(gem) mice than in VDR null mice, demonstrating that mutations abolishing VDR ligand binding result in more severe skeletal defects than VDR null mutations. As gemini ligands induce VDR(gem) transcriptional activity in mice and normalize their serum calcium levels, VDR(gem) is a powerful tool to further unravel both liganded and unliganded VDR signaling.

A vitamin D receptor selectively activated by gemini analogs reveals ligand dependent and independent effects.,Huet T, Laverny G, Ciesielski F, Molnar F, Ramamoorthy TG, Belorusova AY, Antony P, Potier N, Metzger D, Moras D, Rochel N Cell Rep. 2015 Feb 3;10(4):516-26. doi: 10.1016/j.celrep.2014.12.045. Epub 2015, Jan 22. PMID:25620699^[3]

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

References

↑ Ciesielski F, Rochel N, Moras D. Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):235-42. Epub 2007 Jan 10. PMID:17218092 doi:http://dx.doi.org/10.1016/j.jsbmb.2006.12.003
↑ Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J. 1998 Jan 15;17(2):507-19. PMID:9430642 doi:10.1093/emboj/17.2.507
↑ Huet T, Laverny G, Ciesielski F, Molnar F, Ramamoorthy TG, Belorusova AY, Antony P, Potier N, Metzger D, Moras D, Rochel N. A vitamin D receptor selectively activated by gemini analogs reveals ligand dependent and independent effects. Cell Rep. 2015 Feb 3;10(4):516-26. doi: 10.1016/j.celrep.2014.12.045. Epub 2015, Jan 22. PMID:25620699 doi:http://dx.doi.org/10.1016/j.celrep.2014.12.045

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ruo"

@@ Line 1: / Line 1: @@
 ==Crystal structure of zVDR L337H mutant-gemini complex==
-<StructureSection load='4ruo' size='340' side='right' caption='[[4ruo]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
+<StructureSection load='4ruo' size='340' side='right'caption='[[4ruo]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ruo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RUO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RUO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ruo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RUO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RUO FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BIV:21-NOR-9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1,3,25-TRIOL,+20-(4-HYDROXY-4-METHYLPENTYL)-,+(1A,3B,5Z,7E)'>BIV</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hc4|2hc4]], [[2hcd|2hcd]], [[4ruj|4ruj]], [[4rup|4rup]]</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=4ruo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ruo OCA], [http://pdbe.org/4ruo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ruo RCSB], [http://www.ebi.ac.uk/pdbsum/4ruo PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vdra, nr1i1a, vdr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=4ruo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ruo OCA], [http://pdbe.org/4ruo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ruo RCSB], [http://www.ebi.ac.uk/pdbsum/4ruo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ruo ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Brachidanio rerio]]
+[[Category: Large Structures]]
 [[Category: Huet, T]]
 [[Category: Moras, D]]

4ruo

From Proteopedia

Revision as of 10:17, 1 May 2019

Crystal structure of zVDR L337H mutant-gemini complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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