View source for 7utz


==Human thyrotropin analog TR1402 bound to human Thyrotropin receptor in complex with miniGs399 (composite structure)==
<StructureSection load='7utz' size='340' side='right'caption='[[7utz]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7utz]] is a 7 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=7UTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UTZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z41:(2S)-3-hydroxypropane-1,2-diyl+dihexadecanoate'>Z41</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=7utz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7utz OCA], [https://pdbe.org/7utz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7utz RCSB], [https://www.ebi.ac.uk/pdbsum/7utz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7utz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLHA_HUMAN GLHA_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thyroid hormones are vital in metabolism, growth and development(1). Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR)(2). In patients with Graves' disease, autoantibodies that activate the TSHR pathologically increase thyroid hormone activity(3). How autoantibodies mimic thyrotropin function remains unclear. Here we determined cryo-electron microscopy structures of active and inactive TSHR. In inactive TSHR, the extracellular domain lies close to the membrane bilayer. Thyrotropin selects an upright orientation of the extracellular domain owing to steric clashes between a conserved hormone glycan and the membrane bilayer. An activating autoantibody from a patient with Graves' disease selects a similar upright orientation of the extracellular domain. Reorientation of the extracellular domain transduces a conformational change in the seven-transmembrane-segment domain via a conserved hinge domain, a tethered peptide agonist and a phospholipid that binds within the seven-transmembrane-segment domain. Rotation of the TSHR extracellular domain relative to the membrane bilayer is sufficient for receptor activation, revealing a shared mechanism for other glycoprotein hormone receptors that may also extend to other G-protein-coupled receptors with large extracellular domains.

Autoantibody mimicry of hormone action at the thyrotropin receptor.,Faust B, Billesbolle CB, Suomivuori CM, Singh I, Zhang K, Hoppe N, Pinto AFM, Diedrich JK, Muftuoglu Y, Szkudlinski MW, Saghatelian A, Dror RO, Cheng Y, Manglik A Nature. 2022 Sep;609(7928):846-853. doi: 10.1038/s41586-022-05159-1. Epub 2022 , Aug 8. PMID:35940205<ref>PMID:35940205</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7utz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng Y]]
[[Category: Faust B]]
[[Category: Manglik A]]