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- EMDB-34098: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-07... -
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Open data
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Basic information
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Title | Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556, focused on receptor | |||||||||
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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 / regulation of metabolic process / regulation of postsynaptic neurotransmitter receptor internalization / optic nerve development / positive regulation of Rho protein signal transduction / positive regulation of dendritic spine development / : / G-protein alpha-subunit binding / GABA-ergic synapse / positive regulation of stress fiber assembly / myelination / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / neurogenesis / cerebellum development / cell chemotaxis / dendritic shaft / PDZ domain binding / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of neuron projection development / presynaptic membrane / regulation of cell shape / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / G alpha (q) signalling events / postsynaptic membrane / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / dendritic spine / endosome / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / neuronal cell body / glutamatergic synapse / cell surface / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 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 | ![]() | 2.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.2 KB 14.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.9 KB | Display | ![]() |
Images | ![]() | 33 KB | ||
Masks | ![]() | 2.4 MB | ![]() | |
Others | ![]() ![]() | 2.2 MB 2.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yu4MC ![]() 7yu3C ![]() 7yu5C ![]() 7yu6C ![]() 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: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : Human Lysophosphatidic Acid Receptor 1 bound to ONO-0740556
Entire | Name: Human Lysophosphatidic Acid Receptor 1 bound to ONO-0740556 |
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Components |
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-Supramolecule #1: Human Lysophosphatidic Acid Receptor 1 bound to ONO-0740556
Supramolecule | Name: Human Lysophosphatidic Acid Receptor 1 bound to ONO-0740556 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Lysophosphatidic acid receptor 1
Macromolecule | Name: Lysophosphatidic acid receptor 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 42.936004 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DYKDDDDAMG AAISTSIPVI SQPQFTAMNE PQCFYNESIA FFYNRSGKHL ATEWNTVSKL VMGLGITVCI FIMLANLLVM VAIYVNRRF HFPIYYLMAN LAAADFFAGL AYFYLMFNTG PNTRRLTVST WLLRQGLIDT SLTASVANLL AIAIERHITV F RMQLHTRM ...String: DYKDDDDAMG AAISTSIPVI SQPQFTAMNE PQCFYNESIA FFYNRSGKHL ATEWNTVSKL VMGLGITVCI FIMLANLLVM VAIYVNRRF HFPIYYLMAN LAAADFFAGL AYFYLMFNTG PNTRRLTVST WLLRQGLIDT SLTASVANLL AIAIERHITV F RMQLHTRM SNRRVVVVIV VIWTMAIVMG AIPSVGWNCI CDIENCSNMA PLYSDSYLVF WAIFNLVTFV VMVVLYAHIF GY VRQRTMR MSRHSSGPRR NRDTMMSLLK TVVIVLGAFI ICWTPGLVLL LLDVCCPQCD VLAYEKFFLL LAEFNSAMNP IIY SYRDKE MSATFRQILC CQRSENPTGP TEGSDRSASS LNHTILAGVH SNDHSVVENL YFQ |
-Macromolecule #2: [(2~{R})-2-[5-(2-hexylphenyl)pentanoylamino]-3-oxidanyl-propyl] d...
Macromolecule | Name: [(2~{R})-2-[5-(2-hexylphenyl)pentanoylamino]-3-oxidanyl-propyl] dihydrogen phosphate type: ligand / ID: 2 / Number of copies: 1 / Formula: K6L |
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Molecular weight | Theoretical: 415.461 Da |
Chemical component information | ![]() ChemComp-K6L: |
-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 |