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==Crystal structure of zVDR L337H mutant-gemini complex==
==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 ==
== 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 [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.805&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ruo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ruo OCA], [https://pdbe.org/4ruo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ruo RCSB], [https://www.ebi.ac.uk/pdbsum/4ruo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ruo ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/NCOA2_HUMAN 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 ==
== Function ==
[[http://www.uniprot.org/uniprot/VDRA_DANRE 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.<ref>PMID:17218092</ref>  [[http://www.uniprot.org/uniprot/NCOA2_HUMAN 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.<ref>PMID:9430642</ref> 
[https://www.uniprot.org/uniprot/VDRA_DANRE 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.<ref>PMID:17218092</ref>  
<div style="background-color:#fffaf0;">
== 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<ref>PMID:25620699</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ruo" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Huet, T]]
[[Category: Danio rerio]]
[[Category: Moras, D]]
[[Category: Homo sapiens]]
[[Category: Rochel, N]]
[[Category: Large Structures]]
[[Category: Alpha helical sandwich]]
[[Category: Huet T]]
[[Category: Dna]]
[[Category: Moras D]]
[[Category: Ligand]]
[[Category: Rochel N]]
[[Category: Nucleus]]
[[Category: Phosphorylation]]
[[Category: Retinoid x receptor]]
[[Category: Transcription factor]]
[[Category: Transcription factor-transcription regulator complex]]

Latest revision as of 12:55, 1 March 2024

Crystal structure of zVDR L337H mutant-gemini complex

4ruo, resolution 2.81Å

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