View source for 9wp9


==Cryo-EM structure of the d18:1 S1P-bound S1PR3 and Gq complex==
<StructureSection load='9wp9' size='340' side='right'caption='[[9wp9]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wp9]] is a 6 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=9WP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WP9 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]] 3.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S1P:(2S,3R,4E)-2-AMINO-3-HYDROXYOCTADEC-4-EN-1-YL+DIHYDROGEN+PHOSPHATE'>S1P</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=9wp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wp9 OCA], [https://pdbe.org/9wp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wp9 RCSB], [https://www.ebi.ac.uk/pdbsum/9wp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wp9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sphingosine-1-phosphate (S1P) is one of the most extensively studied bioactive lipids that transduces signals via the S1P receptor (S1PR) family (S1PR1-5), a class of G-protein-coupled receptors (GPCRs), to regulate immune cell migration, vascular permeability, and pain modulation. However, the mechanism for achieving specificity in downstream signaling remains poorly understood. Here, we present cryogenic electron microscopic structures of the S1PR3-G(alphaq) complex bound to endogenous agonists: d18:1 S1P or d16:1 S1P. Both agonists shared the same binding pocket and binding mode despite the different signaling intensities of the S1PR3-G(alphaq) signal pathway. By comparing the structures of two agonist-bound complexes, combined with mutagenesis studies, we identified key amino acids, Phe119(3.33) and Arg136(3.50), that play crucial roles in differential agonist recognition and receptor activation. Furthermore, structural comparisons with previously determined S1PR3-G(alphai) complex or G-protein-free S1PR3 structures, along with mutagenesis analysis, revealed dynamic intracellular loop 2 conformations and specific amino acid interactions that contribute to G-protein selectivity. Notably, we identified amino acids at the 34.50 and 34.53 positions within ICL2 as critical for specific interactions with G proteins. These findings provide better understanding of the mechanism of GPCR activation and unique perspectives that can be applied to other class A GPCRs, leading to the possibility of optimized drug development.

Structural insights into the G-protein subtype selectivity revealed by human sphingosine-1-phosphate receptor 3-G(q) complexes.,Yamauchi M, Im D, Maeda S, Ikuta T, Toyomoto M, Asada H, Sugita Y, Kishikawa JI, Noda T, Kato T, Inoue A, Iwata S, Hagiwara M Proc Natl Acad Sci U S A. 2025 Nov 25;122(47):e2507421122. doi: , 10.1073/pnas.2507421122. Epub 2025 Nov 18. PMID:41252158<ref>PMID:41252158</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wp9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Asada H]]
[[Category: Hagiwara M]]
[[Category: Im D]]
[[Category: Iwata S]]
[[Category: Yamauchi M]]