7t9n
From Proteopedia
(Difference between revisions)
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==M22 Agonist Autoantibody bound to Human Thyrotropin receptor in complex with miniGs399 (composite structure)== | ==M22 Agonist Autoantibody bound to Human Thyrotropin receptor in complex with miniGs399 (composite structure)== | ||
| - | <StructureSection load='7t9n' size='340' side='right'caption='[[7t9n]]' scene=''> | + | <StructureSection load='7t9n' size='340' side='right'caption='[[7t9n]], [[Resolution|resolution]] 2.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T9N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7t9n]] 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=7T9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T9N FirstGlance]. <br> |
| - | </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=7t9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9n OCA], [https://pdbe.org/7t9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9n RCSB], [https://www.ebi.ac.uk/pdbsum/7t9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9n ProSAT]</span></td></tr> | + | </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=7t9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9n OCA], [https://pdbe.org/7t9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9n RCSB], [https://www.ebi.ac.uk/pdbsum/7t9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9n ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/A0A0A0MTJ0_HUMAN A0A0A0MTJ0_HUMAN]] Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Plays a central role in controlling thyroid cell metabolism.[RuleBase:RU361222] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Thyroid hormones are vital to metabolism, growth and development(1). Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR)(2). Autoantibodies that activate the TSHR pathologically increase thyroid hormones in Graves' disease(3). How autoantibodies mimic TSH function remains unclear. We determined cryogenic-electron microscopy structures of active and inactive TSHR. In inactive TSHR, the extracellular domain lies close to the membrane bilayer. TSH selects an upright orientation of the extracellular domain due to steric clashes between a conserved hormone glycan and the membrane bilayer. An activating autoantibody from a Graves' disease patient selects a similar upright orientation of the extracellular domain. Reorientation of the extracellular domain transduces a conformational change in the seven transmembrane domain via a conserved hinge domain, a tethered peptide agonist, and a phospholipid that binds within the seven transmembrane 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 Aug 8. pii: 10.1038/s41586-022-05159-1. doi:, 10.1038/s41586-022-05159-1. PMID:35940205<ref>PMID:35940205</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7t9n" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cheng Y]] | [[Category: Cheng Y]] | ||
[[Category: Faust B]] | [[Category: Faust B]] | ||
[[Category: Manglik A]] | [[Category: Manglik A]] | ||
Revision as of 03:17, 8 September 2022
M22 Agonist Autoantibody bound to Human Thyrotropin receptor in complex with miniGs399 (composite structure)
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