View source for 7yqe


==Structure of human SRC regulatory domains in complex with the C-terminal PRRP motifs of GPR54.==
<StructureSection load='7yqe' size='340' side='right'caption='[[7yqe]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7yqe]] is a 2 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=7YQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YQE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</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=7yqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yqe OCA], [https://pdbe.org/7yqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yqe RCSB], [https://www.ebi.ac.uk/pdbsum/7yqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yqe ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for approximately 35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.,Li Z, Yang X, Fu R, Wu Z, Xu S, Jiao J, Qian M, Zhang L, Wu C, Xie T, Yao J, Wu Z, Li W, Ma G, You Y, Chen Y, Zhang HK, Cheng Y, Tang X, Wu P, Lian G, Wei H, Zhao J, Xu J, Ai L, Siwko S, Wang Y, Ding J, Song G, Luo J, Liu M, Xiao J Nat Commun. 2024 Feb 12;15(1):1300. doi: 10.1038/s41467-024-44852-9. PMID:38346942<ref>PMID:38346942</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7yqe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Song G]]
[[Category: Xu S]]