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Yorodumi- PDB-7yu4: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-07... -
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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 | ||||||
Components | Lysophosphatidic acid receptor 1 | ||||||
Keywords | MEMBRANE PROTEIN / GPCR | ||||||
Function / homology | Function and homology information 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 / neurogenesis / positive regulation of stress fiber assembly / myelination / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / 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 / positive regulation of canonical NF-kappaB signal transduction / 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 MAPK cascade / endosome / dendritic spine / 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Akasaka, H. / Shihoya, W. / Nureki, O. | ||||||
Funding support | Japan, 1items
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Citation | Journal: Nat Commun / Year: 2022 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7yu4.cif.gz | 63.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7yu4.ent.gz | 45.6 KB | Display | PDB format |
PDBx/mmJSON format | 7yu4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7yu4_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7yu4_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7yu4_validation.xml.gz | 20 KB | Display | |
Data in CIF | 7yu4_validation.cif.gz | 28.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yu/7yu4 ftp://data.pdbj.org/pub/pdb/validation_reports/yu/7yu4 | 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 (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-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.) Homo sapiens (human) / Gene: LPAR1, EDG2, LPA1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q92633 |
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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 |
-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: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
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) |
-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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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