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- PDB-7yu4: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-07... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7yu4 | ||||||
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Title | Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556, focused on receptor | ||||||
![]() | Lysophosphatidic acid receptor 1 | ||||||
![]() | MEMBRANE PROTEIN / GPCR | ||||||
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 / cellular response to oxygen levels / regulation of metabolic process / negative regulation of cAMP-mediated signaling / 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 / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / myelination / cerebellum development / neurogenesis / cell chemotaxis / dendritic shaft / G protein-coupled receptor activity / PDZ domain binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of neuron projection development / presynaptic membrane / regulation of cell shape / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / 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 | ELECTRON MICROSCOPY / 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 63.8 KB | Display | ![]() |
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PDB format | ![]() | 45.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 20 KB | Display | |
Data in CIF | ![]() | 28.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 34098MC ![]() 7yu3C ![]() 7yu5C ![]() 7yu6C ![]() 7yu7C ![]() 7yu8C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 42936.004 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Chemical | ChemComp-K6L / [( |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human Lysophosphatidic Acid Receptor 1 bound to ONO-0740556 Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: REFMAC / Version: 5.8.0267 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 181071 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.3→88.44 Å / Cor.coef. Fo:Fc: 0.803 / SU B: 32.341 / SU ML: 0.472 / ESU R: 0.592 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Solvent model: PARAMETERS FOR MASK CACLULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 99.316 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Total: 2251 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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