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- EMDB-34100: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-07... -
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Basic information
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Title | Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556, state2 | |||||||||
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Function / homology | ![]() cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Lysosphingolipid and LPA receptors / : / lysophosphatidic acid binding / negative regulation of cilium assembly / regulation of synaptic vesicle cycle / corpus callosum development / bleb assembly ...cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Lysosphingolipid and LPA receptors / : / lysophosphatidic acid binding / negative regulation of cilium assembly / regulation of synaptic vesicle cycle / corpus callosum development / bleb assembly / oligodendrocyte development / negative regulation of cAMP-mediated signaling / cellular response to oxygen levels / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / regulation of metabolic process / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / regulation of postsynaptic neurotransmitter receptor internalization / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / optic nerve development / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of Rho protein signal transduction / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of dendritic spine development / : / photoreceptor outer segment / G-protein alpha-subunit binding / GABA-ergic synapse / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / positive regulation of stress fiber assembly / myelination / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / neurogenesis / cerebellum development / cell chemotaxis / dendritic shaft / Regulation of insulin secretion / G protein-coupled receptor binding / PDZ domain binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
![]() | Akasaka H / Shihoya W / Nureki O | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the active G-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist. Authors: Hiroaki Akasaka / Tatsuki Tanaka / Fumiya K Sano / Yuma Matsuzaki / Wataru Shihoya / Osamu Nureki / ![]() Abstract: Lysophosphatidic acid receptor 1 (LPA) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA is a drug target for various diseases, ...Lysophosphatidic acid receptor 1 (LPA) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA is a drug target for various diseases, including cancer, inflammation, and neuropathic pain. Notably, LPA agonists have potential therapeutic value for obesity and urinary incontinence. Here, we report a cryo-electron microscopy structure of the active human LPA-G complex bound to ONO-0740556, an LPA analog with more potent activity against LPA. Our structure elucidated the details of the agonist binding mode and receptor activation mechanism mediated by rearrangements of transmembrane segment 7 and the central hydrophobic core. A structural comparison of LPA and other phylogenetically-related lipid-sensing GPCRs identified the structural determinants for lipid preference of LPA. Moreover, we characterized the structural polymorphisms at the receptor-G-protein interface, which potentially reflect the G-protein dissociation process. Our study provides insights into the detailed mechanism of LPA binding to agonists and paves the way toward the design of drug-like agonists targeting LPA. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 7.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23 KB 23 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.9 KB | Display | ![]() |
Images | ![]() | 36.5 KB | ||
Masks | ![]() | 7.7 MB | ![]() | |
Others | ![]() ![]() | 7.1 MB 7.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yu6MC ![]() 7yu3C ![]() 7yu4C ![]() 7yu5C ![]() 7yu7C ![]() 7yu8C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.1952 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #1
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-Half map: #2
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Density Histograms |
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Sample components
+Entire : Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556
+Supramolecule #1: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556
+Supramolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #5: Lysophosphatidic Acid Receptor 1
+Supramolecule #6: scFv16
+Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Lysophosphatidic acid receptor 1
+Macromolecule #5: scFv16
+Macromolecule #6: [(2~{R})-2-[5-(2-hexylphenyl)pentanoylamino]-3-oxidanyl-propyl] d...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 7 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |