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Yorodumi- PDB-6btz: Crystal structure of the PI3KC2alpha C2 domain in space group C121 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6btz | ||||||
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Title | Crystal structure of the PI3KC2alpha C2 domain in space group C121 | ||||||
Components | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha | ||||||
Keywords | TRANSFERASE / C2 domain / lipid binding / phosphoinositide / PI3-kinase | ||||||
Function / homology | Function and homology information vascular associated smooth muscle contraction / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the Golgi membrane / clathrin coat assembly / phosphatidylinositol-4-phosphate 3-kinase / membrane organization / phosphatidylinositol biosynthetic process / phosphatidylinositol 3-kinase complex / 1-phosphatidylinositol-4-phosphate 3-kinase activity ...vascular associated smooth muscle contraction / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the Golgi membrane / clathrin coat assembly / phosphatidylinositol-4-phosphate 3-kinase / membrane organization / phosphatidylinositol biosynthetic process / 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 / clathrin binding / 1-phosphatidylinositol-3-kinase activity / positive regulation of cell migration involved in sprouting angiogenesis / Golgi Associated Vesicle Biogenesis / exocytosis / phosphatidylinositol-mediated signaling / Synthesis of PIPs at the plasma membrane / platelet-derived growth factor receptor signaling pathway / positive regulation of autophagy / phosphatidylinositol binding / trans-Golgi network / epidermal growth factor receptor signaling pathway / endocytosis / cell migration / insulin receptor signaling pathway / Clathrin-mediated endocytosis / vesicle / phosphorylation / intracellular membrane-bounded organelle / extracellular exosome / nucleoplasm / ATP binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.85 Å | ||||||
Authors | Chen, K.-E. / Collins, B.M. | ||||||
Citation | Journal: Structure / Year: 2018 Title: Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2α. Authors: Kai-En Chen / Vikas A Tillu / Mintu Chandra / Brett M Collins / Abstract: Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α is essential for many processes, including neuroexocytosis and formation of clathrin-coated ...Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α is essential for many processes, including neuroexocytosis and formation of clathrin-coated vesicles. A defining feature of the class II PI3Ks is a C-terminal module composed of phox-homology (PX) and C2 membrane interacting domains; however, the mechanisms that control their specific cellular localization remain poorly understood. Here we report the crystal structure of the C2 domain of PI3K-C2α in complex with the phosphoinositide head-group mimic inositol hexaphosphate, revealing two distinct pockets for membrane binding. The C2 domain preferentially binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, and low-resolution structures of the combined PX-C2 module by small-angle X-ray scattering reveal a compact conformation in which cooperative lipid binding by each domain binding can occur. Finally, we demonstrate an unexpected role for calcium in perturbing the membrane interactions of the PX-C2 module, which we speculate may be important for regulating the activity of PI3K-C2α. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6btz.cif.gz | 131.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6btz.ent.gz | 100.5 KB | Display | PDB format |
PDBx/mmJSON format | 6btz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bt/6btz ftp://data.pdbj.org/pub/pdb/validation_reports/bt/6btz | HTTPS FTP |
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-Related structure data
Related structure data | 6btyC 6bu0C 6bubC 2b3rS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 14944.179 Da / Num. of mol.: 4 / Fragment: C2 domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3C2A / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: O00443, phosphatidylinositol-4-phosphate 3-kinase #2: Chemical | ChemComp-SO4 / #3: Chemical | ChemComp-O4B / #4: Chemical | ChemComp-GOL / #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.45 Å3/Da / Density % sol: 49.82 % / Mosaicity: 0.21 ° |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: PEG 400, (NH4)2SO4 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 1 Å | ||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 5, 2016 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.85→46.4 Å / Num. obs: 49805 / % possible obs: 99.7 % / Redundancy: 7.4 % / Biso Wilson estimate: 17.38 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.115 / Rpim(I) all: 0.045 / Rrim(I) all: 0.123 / Net I/σ(I): 10.3 / Num. measured all: 368396 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2B3R Resolution: 1.85→46.395 Å / FOM work R set: 0.8586 / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 21.53 / Stereochemistry target values: MLHL
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 64.99 Å2 / Biso mean: 21.61 Å2 / Biso min: 7.71 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.85→46.395 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 18
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