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TitleStructural insights into the engagement of lysophosphatidic acid receptor 1 with different G proteins.
Journal, issue, pagesJ Struct Biol, Vol. 217, Issue 1, Page 108164, Year 2025
Publish dateDec 24, 2024
AuthorsShota Suzuki / Kotaro Tanaka / Akiko Kamegawa / Kouki Nishikawa / Hiroshi Suzuki / Atsunori Oshima / Yoshinori Fujiyoshi /
PubMed AbstractLysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids derived from cell membranes that activate the endothelial differentiation gene family of G protein- ...Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids derived from cell membranes that activate the endothelial differentiation gene family of G protein-coupled receptors. Activation of these receptors triggers multiple downstream signaling cascades through G proteins such as Gi/o, Gq/11, and G12/13. Therefore, LPA and S1P mediate several physiological processes, including cytoskeletal dynamics, neurite retraction, cell migration, cell proliferation, and intracellular ion fluxes. The basis for the G-protein coupling selectivity of EDG receptors, however, remains unknown. Here, we present cryo-electron microscopy structures of LPA-activated LPA1 in complexes with G, G, and G heterotrimers Comparison of the three LPA1-G protein structures shows clearly different conformations of intracellular loop 2 (ICL2) and ICL3 that are likely induced by the different Gα protein interfaces. Interestingly, this G-protein interface interaction is a common feature of LPA and S1P receptors. Our findings provide clues to understanding the promiscuity of G-protein coupling in the endothelial differentiation gene family.
External linksJ Struct Biol / PubMed:39725093
MethodsEM (single particle)
Resolution3.04 - 3.14 Å
Structure data

61031

9izf

EMDB-61031, PDB-9izf:
Cryo-EM structure of LPA1-Gi complex with LPA
Method: EM (single particle) / Resolution: 3.14 Å

61032

9izg

EMDB-61032, PDB-9izg:
Cryo-EM structure of LPA1-Gq complex with LPA
Method: EM (single particle) / Resolution: 3.04 Å

61033

9izh

EMDB-61033, PDB-9izh:
Cryo-EM structure of LPA1-G13 complex with LPA
Method: EM (single particle) / Resolution: 3.04 Å

Chemicals

ChemComp-NKP:
(2R)-2-hydroxy-3-(phosphonooxy)propyl (9E)-octadec-9-enoate

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • mus musculus (house mouse)
  • escherichia coli (E. coli)
KeywordsMEMBRANE PROTEIN / GPCR / SIGNALING PROTEIN

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