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==Crystal Structure of the ligand binding domains of the thyroid receptor:retinoid X receptor complexed with 3,3',5 triiodo-L-thyronine and 9-cis retinoic acid==
==Crystal Structure of the ligand binding domains of the thyroid receptor:retinoid X receptor complexed with 3,3',5 triiodo-L-thyronine and 9-cis retinoic acid==
<StructureSection load='3uvv' size='340' side='right' caption='[[3uvv]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
<StructureSection load='3uvv' size='340' side='right'caption='[[3uvv]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3uvv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UVV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UVV FirstGlance]. <br>
<table><tr><td colspan='2'>[[3uvv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] 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=3UVV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UVV 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>, <scene name='pdbligand=T3:3,5,3TRIIODOTHYRONINE'>T3</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]] 2.95&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">THRA, NR1A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus]), RXRA, NR2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene>, <scene name='pdbligand=T3:3,5,3TRIIODOTHYRONINE'>T3</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=3uvv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uvv RCSB], [http://www.ebi.ac.uk/pdbsum/3uvv 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=3uvv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvv OCA], [https://pdbe.org/3uvv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uvv RCSB], [https://www.ebi.ac.uk/pdbsum/3uvv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uvv ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/THA_CHICK THA_CHICK] Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
Thyroid hormones such as 3,3',5 triiodo-L-thyronine (T3) control numerous aspects of mammalian development and metabolism. The actions of such hormones are mediated by specific thyroid hormone receptors (TRs). TR belongs to the nuclear receptor family of modular transcription factors that binds to specific DNA-response elements within target promoters. These receptors can function as homo- or heterodimers such as TR:9-cis retinoic acid receptor (RXR). Here, we present the atomic resolution structure of the TRalpha*T3:RXRalpha*9-cis retinoic acid (9c) ligand binding domain heterodimer complex at 2.95 A along with T3 hormone binding and dissociation and coactivator binding studies. Our data provide a structural basis for allosteric communication between T3 and 9c and negative cooperativity between their binding pockets. In this structure, both TR and RXR are in the active state conformation for optimal binding to coactivator proteins. However, the structure of TR*T3 within TR*T3:RXR*9c is in a relative state of disorder, and the observed kinetics of binding show that T3 dissociates more rapidly from TR*T3:RXR*9c than from TR*T3:RXR. Also, coactivator binding studies with a steroid receptor coactivator-1 (receptor interaction domains 1-3) fragment show lower affinities (K(a)) for TR*T3:RXR*9c than TR*T3:RXR. Our study corroborates previously reported observations from cell-based and binding studies and offers a structural mechanism for the repression of TR*T3:RXR transactivation by RXR agonists. Furthermore, the recent discoveries of multiple endogenous RXR agonists that mediate physiological tasks such as lipid biosynthesis underscore the pharmacological importance of negative cooperativity in ligand binding within TR:RXR heterodimers.
 
Structural basis for negative cooperativity within agonist-bound TR:RXR heterodimers.,Putcha BD, Wright E, Brunzelle JS, Fernandez EJ Proc Natl Acad Sci U S A. 2012 Apr 2. PMID:22474364<ref>PMID:22474364</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Retinoid X receptor|Retinoid X receptor]]
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
== References ==
*[[Thyroid hormone receptor 3D structures|Thyroid hormone receptor 3D structures]]
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Brunzelle, J S]]
[[Category: Large Structures]]
[[Category: Fernandez, E J]]
[[Category: Brunzelle JS]]
[[Category: Putcha, B D.K]]
[[Category: Fernandez EJ]]
[[Category: Wright, E]]
[[Category: Putcha B-DK]]
[[Category: Allostery]]
[[Category: Wright E]]
[[Category: Alpha helical sandwich]]
[[Category: Hormone receptor-hormone receptor complex]]
[[Category: Tr-rxr heterodimer]]
[[Category: Transactivation]]

Latest revision as of 17:09, 14 March 2024

Crystal Structure of the ligand binding domains of the thyroid receptor:retinoid X receptor complexed with 3,3',5 triiodo-L-thyronine and 9-cis retinoic acidCrystal Structure of the ligand binding domains of the thyroid receptor:retinoid X receptor complexed with 3,3',5 triiodo-L-thyronine and 9-cis retinoic acid

Structural highlights

3uvv is a 2 chain structure with sequence from Gallus gallus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.95Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THA_CHICK Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.

See Also

3uvv, resolution 2.95Å

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