+Open data
-Basic information
Entry | Database: PDB / ID: 8kgg | ||||||
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Title | LPS-bound P2Y10 in complex with G13 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR-G-protein complex | ||||||
Function / homology | Function and homology information D5 dopamine receptor binding / P2Y receptors / regulation of fibroblast migration / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / negative regulation of vascular associated smooth muscle cell migration / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / negative regulation of adenylate cyclase activity / positive regulation of neural precursor cell proliferation ...D5 dopamine receptor binding / P2Y receptors / regulation of fibroblast migration / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / negative regulation of vascular associated smooth muscle cell migration / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / negative regulation of adenylate cyclase activity / positive regulation of neural precursor cell proliferation / regulation of small GTPase mediated signal transduction / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / positive regulation of Rho protein signal transduction / NRAGE signals death through JNK / branching involved in blood vessel morphogenesis / neuronal dense core vesicle / negative regulation of vascular associated smooth muscle cell proliferation / regulation of calcium ion transport / CDC42 GTPase cycle / Rho protein signal transduction / negative regulation of apoptotic signaling pathway / Adenylate cyclase inhibitory pathway / positive regulation of insulin receptor signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / RAC1 GTPase cycle / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / response to nutrient / guanyl-nucleotide exchange factor activity / G protein activity / positive regulation of superoxide anion generation / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / brush border membrane / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / platelet activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / regulation of blood pressure / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / melanosome / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / regulation of cell shape / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / midbody / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / in utero embryonic development / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / cell differentiation / positive regulation of cell migration / G protein-coupled receptor signaling pathway / lysosomal membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.06 Å | ||||||
Authors | He, Y. / Yin, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Chem Biol / Year: 2024 Title: Insights into lysophosphatidylserine recognition and Gα-coupling specificity of P2Y10. Authors: Han Yin / Nozomi Kamakura / Yu Qian / Manae Tatsumi / Tatsuya Ikuta / Jiale Liang / Zhenmei Xu / Ruixue Xia / Anqi Zhang / Changyou Guo / Asuka Inoue / Yuanzheng He / Abstract: The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS, plays crucial roles in the regulation of immune responses and holds promise for the treatment of autoimmune diseases. Here, we ...The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS, plays crucial roles in the regulation of immune responses and holds promise for the treatment of autoimmune diseases. Here, we report the cryoelectron microscopy (cryo-EM) structure of LysoPS-bound P2Y10 in complex with an engineered G heterotrimeric protein. The structure and a mutagenesis study highlight the predominant role of a comprehensive polar network in facilitating the binding and activation of the receptor by LysoPS. This interaction pattern is preserved in GPR174, but not in GPR34. Moreover, our structural study unveils the essential interactions that underlie the Gα engagement of P2Y10 and identifies key determinants for Gα-vs.-Gα-coupling selectivity, whose mutations selectively disrupt Gα engagement while preserving the intact coupling of Gα. The combined structural and functional studies provide insights into the molecular mechanisms of LysoPS recognition and Gα coupling specificity. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8kgg.cif.gz | 213.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8kgg.ent.gz | 167 KB | Display | PDB format |
PDBx/mmJSON format | 8kgg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8kgg_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8kgg_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8kgg_validation.xml.gz | 43.6 KB | Display | |
Data in CIF | 8kgg_validation.cif.gz | 66 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kg/8kgg ftp://data.pdbj.org/pub/pdb/validation_reports/kg/8kgg | HTTPS FTP |
-Related structure data
Related structure data | 37220MC 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
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 26574.400 Da / Num. of mol.: 1 Mutation: C3S,M18E,N22C,R24S,E25R,D26E,G27K,E28T,K29Y,A30V,A31K,E33L,L36I,G42D,E43N,I49F,V50L,K54R,S111D,E114D,I134D,I218A,V221I Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI2, GNAI2B, GNA13 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P04899, UniProt: Q14344 |
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#2: Protein | Mass: 37915.496 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules ER
#3: Antibody | Mass: 26277.299 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) |
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#5: Protein | Mass: 38812.109 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: P2RY10 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O00398 |
#6: Chemical | ChemComp-WJS / ( |
-Details
Has ligand of interest | N |
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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: GPCR/G-protein complex / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Molecular weight | Units: KILODALTONS/NANOMETER / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
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 FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.06 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 238361 / Symmetry type: POINT |