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Open data
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Basic information
Entry | Database: PDB / ID: 7bi2 | ||||||
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Title | PI3KC2aDeltaN and DeltaC-C2 | ||||||
![]() | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha,Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha | ||||||
![]() | TRANSFERASE / PI3KC2 alpha / kinase | ||||||
Function / homology | ![]() negative regulation of zinc ion transmembrane transport / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the Golgi membrane / Synthesis of PIPs at the plasma membrane / autophagosome organization / Golgi Associated Vesicle Biogenesis / phosphatidylinositol-4-phosphate 3-kinase / Clathrin-mediated endocytosis / phosphatidylinositol 3-kinase complex ...negative regulation of zinc ion transmembrane transport / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the Golgi membrane / Synthesis of PIPs at the plasma membrane / autophagosome organization / Golgi Associated Vesicle Biogenesis / phosphatidylinositol-4-phosphate 3-kinase / Clathrin-mediated endocytosis / phosphatidylinositol 3-kinase complex / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / clathrin-coated vesicle / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / clathrin binding / exocytosis / phosphatidylinositol-mediated signaling / cellular response to starvation / phosphatidylinositol binding / macroautophagy / trans-Golgi network / endocytosis / cell migration / vesicle / phosphorylation / ATP binding / nucleus / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Lo, W.T. / Roske, Y. / Daumke, O. / Haucke, V. | ||||||
![]() | ![]() Title: Structural basis of phosphatidylinositol 3-kinase C2α function. Authors: Wen-Ting Lo / Yingyi Zhang / Oscar Vadas / Yvette Roske / Federico Gulluni / Maria Chiara De Santis / Andreja Vujicic Zagar / Heike Stephanowitz / Emilio Hirsch / Fan Liu / Oliver Daumke / ...Authors: Wen-Ting Lo / Yingyi Zhang / Oscar Vadas / Yvette Roske / Federico Gulluni / Maria Chiara De Santis / Andreja Vujicic Zagar / Heike Stephanowitz / Emilio Hirsch / Fan Liu / Oliver Daumke / Misha Kudryashev / Volker Haucke / ![]() ![]() ![]() ![]() Abstract: Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, ...Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 431.3 KB | Display | ![]() |
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PDB format | ![]() | 355.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 760.7 KB | Display | ![]() |
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Full document | ![]() | 771.1 KB | Display | |
Data in XML | ![]() | 36.2 KB | Display | |
Data in CIF | ![]() | 49.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7bi4C ![]() 7bi6C ![]() 7bi9C ![]() 1e8xS ![]() 2iwlS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 131361.906 Da / Num. of mol.: 1 / Mutation: 533-544/GSGS Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q61194, phosphatidylinositol-4-phosphate 3-kinase | ||||
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#2: Chemical | ChemComp-EDO / | ||||
#3: Chemical | ChemComp-17G / | ||||
#4: Chemical | ChemComp-IOD / #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.63 Å3/Da / Density % sol: 53.21 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 0.1MTris, 8% PEG20000, 10% ethylene glycol, 10% formamide |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: May 12, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9184 Å / Relative weight: 1 |
Reflection | Resolution: 3.25→49.2 Å / Num. obs: 22257 / % possible obs: 99.1 % / Redundancy: 4.9 % / CC1/2: 0.998 / Rrim(I) all: 0.152 / Net I/σ(I): 9.73 |
Reflection shell | Resolution: 3.25→3.45 Å / Redundancy: 4.9 % / Mean I/σ(I) obs: 0.84 / Num. unique obs: 3455 / CC1/2: 0.443 / Rrim(I) all: 2.294 / % possible all: 97.1 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 1E8X, 2IWL Resolution: 3.25→49.2 Å / Cor.coef. Fo:Fc: 0.923 / Cor.coef. Fo:Fc free: 0.889 / SU B: 110.025 / SU ML: 0.748 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.647 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 545.73 Å2 / Biso mean: 137.09 Å2 / Biso min: 72.4 Å2
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Refinement step | Cycle: final / Resolution: 3.25→49.2 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.25→3.334 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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