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Yorodumi- PDB-8soe: Phosphoinositide phosphate 3 kinase gamma bound with ADP and two ... -
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-Basic information
Entry | Database: PDB / ID: 8soe | ||||||
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Title | Phosphoinositide phosphate 3 kinase gamma bound with ADP and two Gbetagamma subunits in State 2 | ||||||
Components |
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Keywords | SIGNALING PROTEIN / Phosphoinositide 3-Kinase / Chemotaxis / Cancer | ||||||
Function / homology | Function and homology information Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Activation of the phototransduction cascade / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase complex, class IB / phosphatidylinositol-mediated signaling / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma ...Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Activation of the phototransduction cascade / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase complex, class IB / phosphatidylinositol-mediated signaling / 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 / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / phosphatidylinositol-4,5-bisphosphate 3-kinase / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / phosphatidylinositol phosphate biosynthetic process / 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 / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / kinase activity / cell population proliferation / G protein-coupled receptor signaling pathway / phosphorylation / GTPase activity / protein-containing complex binding / membrane / nucleus / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Bos taurus (cattle) Sus scrofa (pig) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | Chen, C.-L. / Tesmer, J.J.G. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ. Authors: Chun-Liang Chen / Ramizah Syahirah / Sandeep K Ravala / Yu-Chen Yen / Thomas Klose / Qing Deng / John J G Tesmer / Abstract: The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. ...The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. PI3Kγ is activated by Gβγ heterodimers released from G protein-coupled receptors responding to extracellular signals. Here we determined cryo-electron microscopy structures of Sus scrofa PI3Kγ-human Gβγ complexes in the presence of substrates/analogs, revealing two Gβγ binding sites: one on the p110γ helical domain and another on the p101 C-terminal domain. Comparison with PI3Kγ alone reveals conformational changes in the kinase domain upon Gβγ binding that are similar to Ras·GTP-induced changes. Assays of variants perturbing the Gβγ binding sites and interdomain contacts altered by Gβγ binding suggest that Gβγ recruits the enzyme to membranes and allosterically regulates activity via both sites. Studies of zebrafish neutrophil migration align with these findings, paving the way for in-depth investigation of Gβγ-mediated activation mechanisms in this enzyme family and drug development for PI3Kγ. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8soe.cif.gz | 753.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8soe.ent.gz | 616.5 KB | Display | PDB format |
PDBx/mmJSON format | 8soe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/so/8soe ftp://data.pdbj.org/pub/pdb/validation_reports/so/8soe | HTTPS FTP |
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-Related structure data
Related structure data | 40655MC 8so9C 8soaC 8sobC 8socC 8sodC 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: 37416.930 Da / Num. of mol.: 2 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 #2: Protein | | Mass: 127573.531 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Sus scrofa (pig) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A8D1WUA4 #3: Protein | | Mass: 98497.773 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Sus scrofa (pig) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A8D0T2D6 #4: Protein | Mass: 8673.959 Da / Num. of mol.: 2 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 #5: Chemical | ChemComp-ADP / | 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: PI3K-gamma-ADP bound with two Gbetagamma subunits in State 2 Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES | ||||||||||||||||||||||||||||||
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Molecular weight | Value: 210 kDa/nm / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) / Cell: Sf9 / Plasmid: pfastbacdual | ||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: Blot force 2 |
-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 magnification: 81000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Residual tilt: 0.01 mradians |
Image recording | Average exposure time: 3.12 sec. / Electron dose: 55 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) Details: Images were collected in movie-mode at 40 frames per second |
EM imaging optics | Energyfilter name: GIF Quantum ER / Energyfilter slit width: 20 eV |
Image scans | Width: 11520 / Height: 8184 / Movie frames/image: 40 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 181939 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL / Target criteria: correlation coefficient | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1
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