7fii: Difference between revisions
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==== | ==luteinizing hormone/choriogonadotropin receptor-chorionic gonadotropin-Gs complex== | ||
<StructureSection load='7fii' size='340' side='right'caption='[[7fii]]' scene=''> | <StructureSection load='7fii' size='340' side='right'caption='[[7fii]], [[Resolution|resolution]] 4.30Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7fii]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FII 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=7fii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fii OCA], [https://pdbe.org/7fii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fii RCSB], [https://www.ebi.ac.uk/pdbsum/7fii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fii ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.3Å</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=7fii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fii OCA], [https://pdbe.org/7fii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fii RCSB], [https://www.ebi.ac.uk/pdbsum/7fii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fii ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone(1,2). Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs(3-6). They activate the same G-protein-coupled receptor, luteinizing hormone-choriogonadotropin receptor (LHCGR), by binding to the large extracellular domain(3). Here we report four cryo-electron microscopy structures of LHCGR: two structures of the wild-type receptor in the inactive and active states; and two structures of the constitutively active mutated receptor. The active structures are bound to chorionic gonadotropin and the stimulatory G protein (Gs), and one of the structures also contains Org43553, an allosteric agonist(7). The structures reveal a distinct 'push-and-pull' mechanism of receptor activation, in which the extracellular domain is pushed by the bound hormone and pulled by the extended hinge loop next to the transmembrane domain. A highly conserved 10-residue fragment (P10) from the hinge C-terminal loop at the interface between the extracellular domain and the transmembrane domain functions as a tethered agonist to induce conformational changes in the transmembrane domain and G-protein coupling. Org43553 binds to a pocket of the transmembrane domain and interacts directly with P10, which further stabilizes the active conformation. Together, these structures provide a common model for understanding the signalling of glycoprotein hormone receptors and a basis for drug discovery for endocrine diseases. | |||
Structures of full-length glycoprotein hormone receptor signalling complexes.,Duan J, Xu P, Cheng X, Mao C, Croll T, He X, Shi J, Luan X, Yin W, You E, Liu Q, Zhang S, Jiang H, Zhang Y, Jiang Y, Xu HE Nature. 2021 Oct;598(7882):688-692. doi: 10.1038/s41586-021-03924-2. Epub 2021, Sep 22. PMID:34552239<ref>PMID:34552239</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7fii" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bos taurus]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rattus norvegicus]] | ||
[[Category: Cheng X]] | |||
[[Category: Croll T]] | |||
[[Category: Duan J]] | |||
[[Category: He X]] | |||
[[Category: Jiang H]] | |||
[[Category: Jiang Y]] | |||
[[Category: Liu Q]] | |||
[[Category: Luan X]] | |||
[[Category: Mao C]] | |||
[[Category: Shi J]] | |||
[[Category: Xu HE]] | |||
[[Category: Xu P]] | |||
[[Category: Yin W]] | |||
[[Category: You E]] | |||
[[Category: Zhang S]] | |||
[[Category: Zhang Y]] | |||
Latest revision as of 12:25, 9 October 2024
luteinizing hormone/choriogonadotropin receptor-chorionic gonadotropin-Gs complexluteinizing hormone/choriogonadotropin receptor-chorionic gonadotropin-Gs complex
Structural highlights
Publication Abstract from PubMedLuteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone(1,2). Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs(3-6). They activate the same G-protein-coupled receptor, luteinizing hormone-choriogonadotropin receptor (LHCGR), by binding to the large extracellular domain(3). Here we report four cryo-electron microscopy structures of LHCGR: two structures of the wild-type receptor in the inactive and active states; and two structures of the constitutively active mutated receptor. The active structures are bound to chorionic gonadotropin and the stimulatory G protein (Gs), and one of the structures also contains Org43553, an allosteric agonist(7). The structures reveal a distinct 'push-and-pull' mechanism of receptor activation, in which the extracellular domain is pushed by the bound hormone and pulled by the extended hinge loop next to the transmembrane domain. A highly conserved 10-residue fragment (P10) from the hinge C-terminal loop at the interface between the extracellular domain and the transmembrane domain functions as a tethered agonist to induce conformational changes in the transmembrane domain and G-protein coupling. Org43553 binds to a pocket of the transmembrane domain and interacts directly with P10, which further stabilizes the active conformation. Together, these structures provide a common model for understanding the signalling of glycoprotein hormone receptors and a basis for drug discovery for endocrine diseases. Structures of full-length glycoprotein hormone receptor signalling complexes.,Duan J, Xu P, Cheng X, Mao C, Croll T, He X, Shi J, Luan X, Yin W, You E, Liu Q, Zhang S, Jiang H, Zhang Y, Jiang Y, Xu HE Nature. 2021 Oct;598(7882):688-692. doi: 10.1038/s41586-021-03924-2. Epub 2021, Sep 22. PMID:34552239[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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