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Open data
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Basic information
Entry | Database: PDB / ID: 8soa | ||||||
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Title | Phosphoinositide phosphate 3 kinase gamma bound with ATP | ||||||
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Function / homology | ![]() 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase complex, class IB / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Chen, C.-L. / Tesmer, J.J.G. | ||||||
Funding support | ![]()
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![]() | ![]() 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 587 KB | Display | ![]() |
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PDB format | ![]() | 476.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 40651MC ![]() 8so9C ![]() 8sobC ![]() 8socC ![]() 8sodC ![]() 8soeC 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: 127573.531 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
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#2: Protein | Mass: 98497.773 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
#3: Chemical | ChemComp-ATP / ![]() |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: PI3K-gamma-ATP / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Value: 210 kDa/nm / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | |||||||||||||||||||||||||
Specimen support | Details: Glow discharge for 60s / 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 |
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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![]() ![]() |
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![]() |
Image scans | Width: 11520 / Height: 8184 / Movie frames/image: 40 |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 200533 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL / Target criteria: correlation coefficient | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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