3uvv

From Proteopedia

(Difference between revisions)

Revision as of 09:07, 15 November 2023

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

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.

Publication Abstract from PubMed

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^[1]

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

References

↑ Putcha BD, Wright E, Brunzelle JS, Fernandez EJ. Structural basis for negative cooperativity within agonist-bound TR:RXR heterodimers. Proc Natl Acad Sci U S A. 2012 Apr 2. PMID:22474364 doi:10.1073/pnas.1119852109

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/3uvv"

@@ Line 3: / Line 3: @@
 <StructureSection load='3uvv' size='340' side='right'caption='[[3uvv]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3uvv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chick Chick] and [https://en.wikipedia.org/wiki/Human Human]. 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>
+<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" id="ligandDat"><scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</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 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK]), RXRA, NR2B1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[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>
 == Function ==
-[[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. [[https://www.uniprot.org/uniprot/RXRA_HUMAN RXRA_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 RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. 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 of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.<ref>PMID:10195690</ref> <ref>PMID:11162439</ref> <ref>PMID:11915042</ref> <ref>PMID:20215566</ref>
+[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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Chick]]
+[[Category: Gallus gallus]]
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Brunzelle, J S]]
+[[Category: Brunzelle JS]]
-[[Category: Fernandez, E J]]
+[[Category: Fernandez EJ]]
-[[Category: Putcha, B D.K]]
+[[Category: Putcha B-DK]]
-[[Category: Wright, E]]
+[[Category: Wright E]]
-[[Category: Allostery]]
-[[Category: Alpha helical sandwich]]
-[[Category: Hormone receptor-hormone receptor complex]]
-[[Category: Tr-rxr heterodimer]]
-[[Category: Transactivation]]

3uvv

From Proteopedia

Revision as of 09:07, 15 November 2023

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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