4dm8: Difference between revisions
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<StructureSection load='4dm8' size='340' side='right'caption='[[4dm8]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='4dm8' size='340' side='right'caption='[[4dm8]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4dm8]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4dm8]] is a 4 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=4DM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DM8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=REA:RETINOIC+ACID'>REA</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=REA:RETINOIC+ACID'>REA</scene></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=4dm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dm8 OCA], [https://pdbe.org/4dm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dm8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dm8 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/RARB_HUMAN RARB_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.<ref>PMID:12554770</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Retinoic acid receptor|Retinoic acid receptor]] | *[[Retinoic acid receptor 3D structures|Retinoic acid receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bourguet | [[Category: Bourguet W]] | ||
[[Category: Cura | [[Category: Br livet Y]] | ||
[[Category: Eiler | [[Category: Cura V]] | ||
[[Category: Moras | [[Category: Eiler S]] | ||
[[Category: Osz | [[Category: Moras D]] | ||
[[Category: Peluso-Iltis | [[Category: Osz J]] | ||
[[Category: Rochel | [[Category: Peluso-Iltis C]] | ||
[[Category: Ruff | [[Category: Rochel N]] | ||
[[Category: Ruff M]] | |||
Revision as of 11:27, 21 September 2022
Crystal structure of RARb LBD in complex with 9cis retinoic acidCrystal structure of RARb LBD in complex with 9cis retinoic acid
Structural highlights
Function[RARB_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.[1] Publication Abstract from PubMedTranscription regulation by steroid hormones, vitamin derivatives, and metabolites is mediated by nuclear receptors (NRs), which play an important role in ligand-dependent gene expression and human health. NRs function as homodimers or heterodimers and are involved in a combinatorial, coordinated and sequentially orchestrated exchange between coregulators (corepressors, coactivators). The architecture of DNA-bound functional dimers positions the coregulators proteins. We previously demonstrated that retinoic acid (RAR-RXR) and vitamin D3 receptors (VDR-RXR) heterodimers recruit only one coactivator molecule asymmetrically without steric hindrance for the binding of a second cofactor. We now address the problem of homodimers for which the presence of two identical targets enhances the functional importance of the mode of binding. Using structural and biophysical methods and RAR as a model, we could dissect the molecular mechanism of coactivator recruitment to homodimers. Our study reveals an allosteric mechanism whereby binding of a coactivator promotes formation of nonsymmetrical RAR homodimers with a 21 stoichiometry. Ligand conformation and the cofactor binding site of the unbound receptor are affected through the dimer interface. A similar control mechanism is observed with estrogen receptor (ER) thus validating the negative cooperativity model for an established functional homodimer. Correlation with published data on other NRs confirms the general character of this regulatory pathway. Structural basis for a molecular allosteric control mechanism of cofactor binding to nuclear receptors.,Osz J, Brelivet Y, Peluso-Iltis C, Cura V, Eiler S, Ruff M, Bourguet W, Rochel N, Moras D Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):E588-94. Epub 2012 Feb 21. PMID:22355136[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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