View source for 3gws


==Crystal Structure of T3-Bound Thyroid Hormone Receptor==
<StructureSection load='3gws' size='340' side='right'caption='[[3gws]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gws]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2h6w 2h6w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GWS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GWS 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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=3gws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gws OCA], [https://pdbe.org/3gws PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gws RCSB], [https://www.ebi.ac.uk/pdbsum/3gws PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gws 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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gw/3gws_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gws ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The thyroid hormone receptor (TR) D-domain links the ligand-binding domain (LBD, EF-domain) to the DNA-binding domain (DBD, C-domain), but its structure, and even its existence as a functional unit, are controversial. The D domain is poorly conserved throughout the nuclear receptor family and was originally proposed to comprise an unfolded hinge that facilitates rotation between the LBD and the DBD. Previous TR LBD structures, however, have indicated that the true unstructured region is three to six amino acid residues long and that the D-domain N terminus folds into a short amphipathic alpha-helix (H0) contiguous with the DBD and that the C terminus of the D-domain comprises H1 and H2 of the LBD. Here, we solve structures of TR-LBDs in different crystal forms and show that the N terminus of the TRalpha D-domain can adopt two structures; it can either fold into an amphipathic helix that resembles TRbeta H0 or form an unstructured loop. H0 formation requires contacts with the AF-2 coactivator-binding groove of the neighboring TR LBD, which binds H0 sequences that resemble coactivator LXXLL motifs. Structural analysis of a liganded TR LBD with small angle X-ray scattering (SAXS) suggests that AF-2/H0 interactions mediate dimerization of this protein in solution. We propose that the TR D-domain has the potential to form functionally important extensions of the DBD and LBD or unfold to permit TRs to adapt to different DNA response elements. We also show that mutations of the D domain LXXLL-like motif indeed selectively inhibit TR interactions with an inverted palindromic response element (F2) in vitro and TR activity at this response element in cell-based transfection experiments.

Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function.,Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Neto M, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov I J Mol Biol. 2006 Jul 14;360(3):586-98. Epub 2006 May 19. PMID:16781732<ref>PMID:16781732</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gws" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thyroid hormone receptor|Thyroid hormone receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aparicio R]]
[[Category: Baxter JD]]
[[Category: Dias SMG]]
[[Category: Nascimento AS]]
[[Category: Nunes FM]]
[[Category: Polikarpov I]]
[[Category: Webb P]]