7td2: Difference between revisions
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==== | ==Lysophosphatidic acid receptor 1-Gi complex bound to LPA, state a== | ||
<StructureSection load='7td2' size='340' side='right'caption='[[7td2]]' scene=''> | <StructureSection load='7td2' size='340' side='right'caption='[[7td2]], [[Resolution|resolution]] 3.11Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7td2]] 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=7TD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TD2 FirstGlance]. <br> | ||
</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=7td2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7td2 OCA], [https://pdbe.org/7td2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7td2 RCSB], [https://www.ebi.ac.uk/pdbsum/7td2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7td2 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.11Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NKP:(2R)-2-HYDROXY-3-(PHOSPHONOOXY)PROPYL+(9E)-OCTADEC-9-ENOATE'>NKP</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=7td2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7td2 OCA], [https://pdbe.org/7td2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7td2 RCSB], [https://www.ebi.ac.uk/pdbsum/7td2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7td2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/LPAR1_HUMAN LPAR1_HUMAN] Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Stimulates phospholipase C (PLC) activity in a manner that is dependent on RALA activation.<ref>PMID:19306925</ref> | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7td2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lysophosphatidic acid receptor|Lysophosphatidic acid receptor]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bos taurus]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[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]] | |||
Latest revision as of 14:33, 23 October 2024
Lysophosphatidic acid receptor 1-Gi complex bound to LPA, state aLysophosphatidic acid receptor 1-Gi complex bound to LPA, state a
Structural highlights
FunctionLPAR1_HUMAN Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Stimulates phospholipase C (PLC) activity in a manner that is dependent on RALA activation.[1] Publication Abstract from PubMedLysophospholipids 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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