+Open data
-Basic information
Entry | Database: PDB / ID: 7td3 | ||||||||||||
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Title | Sphingosine-1-phosphate receptor 1-Gi complex bound to S1P | ||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR / complex / lipid | ||||||||||||
Function / homology | Function and homology information Adenylate cyclase inhibitory pathway / cardiac muscle tissue growth involved in heart morphogenesis / Adrenaline,noradrenaline inhibits insulin secretion / sphingosine-1-phosphate receptor activity / ADP signalling through P2Y purinoceptor 12 / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / T cell migration / Extra-nuclear estrogen signaling ...Adenylate cyclase inhibitory pathway / cardiac muscle tissue growth involved in heart morphogenesis / Adrenaline,noradrenaline inhibits insulin secretion / sphingosine-1-phosphate receptor activity / ADP signalling through P2Y purinoceptor 12 / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / T cell migration / Extra-nuclear estrogen signaling / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (i) signalling events / endothelial cell differentiation / heart trabecula morphogenesis / Activation of the phototransduction cascade / regulation of metabolic process / regulation of bone mineralization / sphingosine-1-phosphate receptor signaling pathway / leukocyte chemotaxis / negative regulation of synaptic transmission / regulation of bone resorption / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GTPase activating protein binding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / positive regulation of positive chemotaxis / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / lamellipodium assembly / G alpha (q) signalling events / negative regulation of stress fiber assembly / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / transmission of nerve impulse / 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 cell adhesion / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled receptor binding / G protein-coupled receptor activity / positive regulation of smooth muscle cell proliferation / brain development / 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 / neuron differentiation / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / G-protein beta-subunit binding / GDP binding / heterotrimeric G-protein complex / chemotaxis / cell migration / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / actin cytoskeleton organization / angiogenesis / Interleukin-4 and Interleukin-13 signaling / cell population proliferation / Potential therapeutics for SARS / cell adhesion / endosome / positive regulation of cell migration / cell cycle / membrane raft / G protein-coupled receptor signaling pathway / cell division / external side of plasma membrane / intracellular membrane-bounded organelle / GTPase activity Similarity search - Function | ||||||||||||
Biological species | Bos taurus (cattle) Rattus norvegicus (Norway rat) Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||||||||
Authors | Liu, S. / Paknejad, N. / Zhu, L. / Kihara, Y. / Ray, D. / Chun, J. / Liu, W. / Hite, R.K. / Huang, X.Y. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Nat Commun / Year: 2022 Title: Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate. Authors: Shian Liu / Navid Paknejad / Lan Zhu / Yasuyuki Kihara / Manisha Ray / Jerold Chun / Wei Liu / Richard K Hite / Xin-Yun Huang / Abstract: Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). ...Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR-G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P) and heterotrimeric G complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA) and G complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P-targeting drugs. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7td3.cif.gz | 187.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7td3.ent.gz | 148.1 KB | Display | PDB format |
PDBx/mmJSON format | 7td3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/td/7td3 ftp://data.pdbj.org/pub/pdb/validation_reports/td/7td3 | HTTPS FTP |
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-Related structure data
Related structure data | 25822MC 7td0C 7td1C 7td2C 7td4C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BAG
#1: Protein | Mass: 37416.930 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62871 |
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#2: Protein | Mass: 43163.070 Da / Num. of mol.: 1 / Mutation: G203A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnai1, Gnai-1 / Production host: Escherichia coli (E. coli) / References: UniProt: B2RSH2 |
#3: Protein | Mass: 7845.078 Da / Num. of mol.: 1 / Mutation: C68S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
-Protein / Non-polymers / Sugars , 3 types, 3 molecules R
#4: Protein | Mass: 43938.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: S1PR1, CHEDG1, EDG1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P21453 |
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#5: Chemical | ChemComp-S1P / ( |
#6: Sugar | ChemComp-NAG / |
-Details
Has ligand of interest | Y |
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-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: complex of Sphingosine-1-phosphate receptor 1 with G-protein and S1P Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES | ||||||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7 | ||||||||||||||||
Specimen | 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 FIELDBright-field microscopy / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 24.65 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 449331 / Symmetry type: POINT |