View source for 4zo1


==Crystal Structure of the T3-bound TR-beta Ligand-binding Domain in complex with RXR-alpha==
<StructureSection load='4zo1' size='340' side='right'caption='[[4zo1]], [[Resolution|resolution]] 3.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zo1]] is a 3 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=4ZO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZO1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.221&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4zo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zo1 OCA], [https://pdbe.org/4zo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zo1 RCSB], [https://www.ebi.ac.uk/pdbsum/4zo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zo1 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN] Defects in THRB are the cause of generalized thyroid hormone resistance (GTHR) [MIM:[https://omim.org/entry/188570 188570]. GTHR is a disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH).<ref>PMID:2510172</ref> <ref>PMID:2153155</ref> <ref>PMID:1846005</ref> <ref>PMID:1661299</ref> <ref>PMID:1653889</ref> <ref>PMID:1563081</ref> <ref>PMID:1314846</ref> <ref>PMID:1619012</ref> <ref>PMID:1587388</ref> <ref>PMID:1324420</ref> <ref>PMID:8514853</ref> <ref>PMID:8175986</ref> <ref>PMID:7833659</ref> <ref>PMID:8664910</ref> <ref>PMID:8889584</ref> <ref>PMID:10660344</ref> <ref>PMID:16804041</ref> <ref>PMID:19268523</ref>   Defects in THRB are the cause of generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:[https://omim.org/entry/274300 274300]. An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone.  Defects in THRB are the cause of selective pituitary thyroid hormone resistance (PRTH) [MIM:[https://omim.org/entry/145650 145650]; also known as familial hyperthyroidism due to inappropriate thyrotropin secretion. PRTH is a variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established.<ref>PMID:7528740</ref> <ref>PMID:8381821</ref> 
== Function ==
[https://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN] High affinity receptor for triiodothyronine.<ref>PMID:17418816</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A subset of nuclear receptors (NRs) function as obligate heterodimers with retinoid X receptor (RXR), allowing integration of ligand-dependent signals across the dimer interface via an unknown structural mechanism. Using nuclear magnetic resonance (NMR) spectroscopy, x-ray crystallography and hydrogen/deuterium exchange (HDX) mass spectrometry, here we show an allosteric mechanism through which RXR co-operates with a permissive dimer partner, peroxisome proliferator-activated receptor (PPAR)-gamma, while rendered generally unresponsive by a non-permissive dimer partner, thyroid hormone (TR) receptor. Amino acid residues that mediate this allosteric mechanism comprise an evolutionarily conserved network discovered by statistical coupling analysis (SCA). This SCA network acts as a signalling rheostat to integrate signals between dimer partners, ligands and coregulator-binding sites, thereby affecting signal transmission in RXR heterodimers. These findings define rules guiding how NRs integrate two ligand-dependent signalling pathways into RXR heterodimer-specific responses.

Structural mechanism for signal transduction in RXR nuclear receptor heterodimers.,Kojetin DJ, Matta-Camacho E, Hughes TS, Srinivasan S, Nwachukwu JC, Cavett V, Nowak J, Chalmers MJ, Marciano DP, Kamenecka TM, Shulman AI, Rance M, Griffin PR, Bruning JB, Nettles KW Nat Commun. 2015 Aug 20;6:8013. doi: 10.1038/ncomms9013. PMID:26289479<ref>PMID:26289479</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zo1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
*[[Thyroid hormone receptor|Thyroid hormone receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bruning JB]]
[[Category: Cavett V]]
[[Category: Chalmers MJ]]
[[Category: Griffin PR]]
[[Category: Hughes TS]]
[[Category: Kamenecka TM]]
[[Category: Kojetin DJ]]
[[Category: Mangelsdorf DJ]]
[[Category: Marciano DP]]
[[Category: Matta-Camacho E]]
[[Category: Nettles KW]]
[[Category: Nowak J]]
[[Category: Nwachukwu JC]]
[[Category: Rance M]]
[[Category: Shulman AI]]
[[Category: Srinivasan S]]