9l9o: Difference between revisions
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==Cryo-EM structure of apo GPR50 with BRIL fusion, anti-BRIL Fab, and anti-Fab Nb complex== | |||
<StructureSection load='9l9o' size='340' side='right'caption='[[9l9o]], [[Resolution|resolution]] 2.98Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9l9o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9L9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9L9O 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]] 2.98Å</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=9l9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9l9o OCA], [https://pdbe.org/9l9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9l9o RCSB], [https://www.ebi.ac.uk/pdbsum/9l9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9l9o ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
GPR50 is an orphan GPCR that belongs to the member of melatonin-related receptor family. GPR50 plays roles in various physiological processes, including cancer progression, Notch signaling, and insulin, leptin, and glucocorticoid signaling. GPR50 forms a complex with melatonin receptor type 1A or 1B, and regulates signaling activity of melatonin receptor type 1A. Although endogenous agonists have not been characterized, GPR50 may have its own signaling activity, which is undefined at present. In this study, in an attempt to characterize the orphan activity of GPR50, we determined the 3.4 A structure of ligand-free GPR50 using cryo-electron microscopy. We showed that GPR50 exhibits moderate constitutive activity through interaction with Galpha(12). The structure reveals a putative ligand binding pocket and ligand access channels of GPR50 that differ from those of melatonin receptors. Based on the comparison with the AlphaFold3-predicted active state, we propose an activation mechanism of GPR50. Our findings could serve as a platform in identifying the synthetic or endogenous ligands of GPR50, providing insights into the elusive G-protein-dependent signaling of GPR50. | |||
Structure of the melatonin-related orphan receptor, GPR50.,Shin J, Baek D, Kim J, Park J, Jeong E, Kim Y, Kim YJ, Cho Y Mol Cells. 2026 Feb 8:100331. doi: 10.1016/j.mocell.2026.100331. PMID:41666959<ref>PMID:41666959</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9l9o" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Cho Y]] | |||
[[Category: Shin J]] | |||
