8w8s: Difference between revisions
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New page: '''Unreleased structure''' The entry 8w8s is ON HOLD Authors: Sun, J.P., Yu, X., Gao, N., Yang, F., Wang, J.Y., Yang, Z., Guan, Y., Wang, G.P. Description: Cryo-EM structure of the AA1... |
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==Cryo-EM structure of the AA14-bound GPR101 complex== | |||
<StructureSection load='8w8s' size='340' side='right'caption='[[8w8s]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8w8s]] is a 1 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=8W8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8W8S 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]] 3.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U7D:1-(4-methylpyridin-2-yl)-3-[3-(trifluoromethyl)phenyl]thiourea'>U7D</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=8w8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8w8s OCA], [https://pdbe.org/8w8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8w8s RCSB], [https://www.ebi.ac.uk/pdbsum/8w8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8w8s ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential. | |||
Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.,Yang Z, Wang JY, Yang F, Zhu KK, Wang GP, Guan Y, Ning SL, Lu Y, Li Y, Zhang C, Zheng Y, Zhou SH, Wang XW, Wang MW, Xiao P, Yi F, Zhang C, Zhang PJ, Xu F, Liu BH, Zhang H, Yu X, Gao N, Sun JP Nat Chem Biol. 2024 Apr;20(4):484-492. doi: 10.1038/s41589-023-01456-6. Epub 2023 , Nov 9. PMID:37945893<ref>PMID:37945893</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8w8s" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Sun | <references/> | ||
[[Category: Wang | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Yang | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Gao N]] | ||
[[Category: Guan Y]] | |||
[[Category: Sun JP]] | |||
[[Category: Wang GP]] | |||
[[Category: Wang JY]] | |||
[[Category: Yang F]] | |||
[[Category: Yang Z]] | |||
[[Category: Yu X]] | |||
Latest revision as of 10:03, 17 October 2024
Cryo-EM structure of the AA14-bound GPR101 complex
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