View source for 8xbg


==Human GPR34 -Gi complex bound to S3E-LysoPS, receptor focused==
<StructureSection load='8xbg' size='340' side='right'caption='[[8xbg]], [[Resolution|resolution]] 3.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8xbg]] 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=8XBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XBG 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]] 3.43&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KW0:(2~{S})-2-azanyl-3-[[(2~{R})-1-ethoxy-3-[(~{Z})-octadec-9-enoyl]oxy-propan-2-yl]oxy-oxidanyl-phosphoryl]oxy-propanoic+acid'>KW0</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=8xbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xbg OCA], [https://pdbe.org/8xbg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xbg RCSB], [https://www.ebi.ac.uk/pdbsum/8xbg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xbg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GPR34_HUMAN GPR34_HUMAN] Orphan receptor.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-G(i) complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.

Structural basis for lysophosphatidylserine recognition by GPR34.,Izume T, Kawahara R, Uwamizu A, Chen L, Yaginuma S, Omi J, Kawana H, Hou F, Sano FK, Tanaka T, Kobayashi K, Okamoto HH, Kise Y, Ohwada T, Aoki J, Shihoya W, Nureki O Nat Commun. 2024 Feb 7;15(1):902. doi: 10.1038/s41467-024-45046-z. PMID:38326347<ref>PMID:38326347</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8xbg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kawahara R]]
[[Category: Nureki O]]
[[Category: Shihoya W]]