View source for 7td4


==Sphingosine-1-phosphate receptor 1-Gi complex bound to Siponimod==
<StructureSection load='7td4' size='340' side='right'caption='[[7td4]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7td4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TD4 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J8C:1-[[4-[(~{E})-~{N}-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-~{C}-methyl-carbonimidoyl]-2-ethyl-phenyl]methyl]azetidine-3-carboxylic+acid'>J8C</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7td4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7td4 OCA], [https://pdbe.org/7td4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7td4 RCSB], [https://www.ebi.ac.uk/pdbsum/7td4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7td4 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR-G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P(1)) and heterotrimeric G(i) complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA(1)) and G(i) complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P(1)-targeting drugs.

Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate.,Liu S, Paknejad N, Zhu L, Kihara Y, Ray M, Chun J, Liu W, Hite RK, Huang XY Nat Commun. 2022 Feb 8;13(1):731. doi: 10.1038/s41467-022-28417-2. PMID:35136060<ref>PMID:35136060</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7td4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Chun J]]
[[Category: Hite RK]]
[[Category: Huang XY]]
[[Category: Kihara Y]]
[[Category: Liu S]]
[[Category: Liu W]]
[[Category: Paknejad N]]
[[Category: Ray D]]
[[Category: Zhu L]]