[English] 日本語
Yorodumi- PDB-4cak: Three-dimensional reconstruction of intact human integrin alphaII... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4cak | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Three-dimensional reconstruction of intact human integrin alphaIIbbeta3 in a phospholipid bilayer nanodisc | ||||||||||||
Components |
| ||||||||||||
Keywords | CELL ADHESION / INTEGRIN / SINGLE PARTICLE RECONSTRUCTION | ||||||||||||
Function / homology | Function and homology information tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / integrin alphaIIb-beta3 complex / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / regulation of extracellular matrix organization / platelet alpha granule membrane ...tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / integrin alphaIIb-beta3 complex / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / regulation of extracellular matrix organization / platelet alpha granule membrane / positive regulation of glomerular mesangial cell proliferation / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / fibrinogen binding / maintenance of postsynaptic specialization structure / alphav-beta3 integrin-HMGB1 complex / blood coagulation, fibrin clot formation / vascular endothelial growth factor receptor 2 binding / negative regulation of lipid transport / glycinergic synapse / negative regulation of low-density lipoprotein receptor activity / angiogenesis involved in wound healing / Elastic fibre formation / regulation of release of sequestered calcium ion into cytosol / mesodermal cell differentiation / cell-substrate junction assembly / alphav-beta3 integrin-IGF-1-IGF1R complex / platelet-derived growth factor receptor binding / filopodium membrane / extracellular matrix binding / positive regulation of fibroblast migration / regulation of postsynaptic neurotransmitter receptor internalization / positive regulation of vascular endothelial growth factor receptor signaling pathway / apolipoprotein A-I-mediated signaling pathway / regulation of bone resorption / apoptotic cell clearance / negative regulation of macrophage derived foam cell differentiation / positive regulation of cell adhesion mediated by integrin / wound healing, spreading of epidermal cells / heterotypic cell-cell adhesion / negative regulation of lipid storage / integrin complex / Molecules associated with elastic fibres / positive regulation of leukocyte migration / cellular response to insulin-like growth factor stimulus / positive regulation of cell-matrix adhesion / smooth muscle cell migration / cell adhesion mediated by integrin / microvillus membrane / positive regulation of bone resorption / negative chemotaxis / Syndecan interactions / p130Cas linkage to MAPK signaling for integrins / cellular response to platelet-derived growth factor stimulus / activation of protein kinase activity / cell-substrate adhesion / protein disulfide isomerase activity / positive regulation of smooth muscle cell migration / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / GRB2:SOS provides linkage to MAPK signaling for Integrins / platelet-derived growth factor receptor signaling pathway / fibronectin binding / ECM proteoglycans / positive regulation of T cell migration / Integrin cell surface interactions / coreceptor activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / Signal transduction by L1 / cell adhesion molecule binding / positive regulation of endothelial cell proliferation / embryo implantation / positive regulation of endothelial cell migration / Integrin signaling / substrate adhesion-dependent cell spreading / positive regulation of smooth muscle cell proliferation / cell-matrix adhesion / response to activity / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / protein kinase C binding / cell-cell adhesion / ruffle membrane / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / wound healing / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / cellular response to mechanical stimulus / platelet activation / platelet aggregation / VEGFA-VEGFR2 Pathway / positive regulation of fibroblast proliferation / integrin binding / cellular response to xenobiotic stimulus / positive regulation of angiogenesis / Signaling by RAF1 mutants Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / negative staining / Resolution: 20.5 Å | ||||||||||||
Authors | Choi, W.S. / Rice, W.J. / Stokes, D.L. / Coller, B.S. | ||||||||||||
Citation | Journal: Blood / Year: 2013 Title: Three-dimensional reconstruction of intact human integrin αIIbβ3: new implications for activation-dependent ligand binding. Authors: Won-Seok Choi / William J Rice / David L Stokes / Barry S Coller / Abstract: Integrin αIIbβ3 plays a central role in hemostasis and thrombosis. We provide the first 3-dimensional reconstruction of intact purified αIIbβ3 in a nanodisc lipid bilayer. Unlike previous models, ...Integrin αIIbβ3 plays a central role in hemostasis and thrombosis. We provide the first 3-dimensional reconstruction of intact purified αIIbβ3 in a nanodisc lipid bilayer. Unlike previous models, it shows that the ligand-binding head domain is on top, pointing away from the membrane. Moreover, unlike the crystal structure of the recombinant ectodomain, the lower legs are not parallel, straight, and adjacent. Rather, the αIIb lower leg is bent between the calf-1 and calf-2 domains and the β3 Integrin-Epidermal Growth Factor (I-EGF) 2 to 4 domains are freely coiled rather than in a cleft between the β3 headpiece and the αIIb lower leg. Our data indicate an important role for the region that links the distal calf-2 and β-tail domains to their respective transmembrane (TM) domains in transmitting the conformational changes in the TM domains associated with inside-out activation. | ||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 4cak.cif.gz | 426.4 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4cak.ent.gz | 299.9 KB | Display | PDB format |
PDBx/mmJSON format | 4cak.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4cak_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4cak_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 4cak_validation.xml.gz | 120 KB | Display | |
Data in CIF | 4cak_validation.cif.gz | 159.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ca/4cak ftp://data.pdbj.org/pub/pdb/validation_reports/ca/4cak | HTTPS FTP |
-Related structure data
Related structure data | 2281MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 104460.719 Da / Num. of mol.: 1 / Fragment: ECTODOMAIN, UNP RESIDUES 32-990 / Source method: isolated from a natural source / Details: FITTED FROM PDB ID 3FCS / Source: (natural) Homo sapiens (human) / Tissue: BLOOD / References: UniProt: P08514 |
---|---|
#2: Protein | Mass: 76316.945 Da / Num. of mol.: 1 / Fragment: RESIDUES 27-716 / Source method: isolated from a natural source / Details: FITTED FROM PDB ID 3FCS / Source: (natural) Homo sapiens (human) / Cell line: PLATELET / Tissue: BLOOD / References: UniProt: P05106 |
-Sugars , 5 types, 7 molecules
#3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #5: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #6: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Sugar | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: INTEGRIN ALPHAIIBBETA3 IN LIPID BILAYER NANODISC / Type: COMPLEX / Details: MICROGRAPHS TAKEN ON CCD |
---|---|
Buffer solution | Name: 150 MM NACL, 10 MM HEPES, PH 7.4, 1 MM CACL2 AND 1 MM MGCL2 pH: 7.4 Details: 150 MM NACL, 10 MM HEPES, PH 7.4, 1 MM CACL2 AND 1 MM MGCL2 |
Specimen | Conc.: 0.02 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: YES / Vitrification applied: NO |
EM staining | Type: NEGATIVE / Material: uranyl acetate |
Specimen support | Details: CARBON |
Vitrification | Details: VITRIFICATION 1 -- CRYOGEN- NONE, INSTRUMENT- NONE, |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TECNAI F20 / Date: Feb 1, 2010 Details: LOW DOSE PACKAGE USED. CCD MAGNIFICATION IS 1.76 TIMES FILM MAGNIFICATION |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 120 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 29000 X / Calibrated magnification: 50592 X / Nominal defocus max: 1500 nm / Nominal defocus min: 1200 nm / Cs: 2 mm |
Specimen holder | Tilt angle max: 50 ° / Tilt angle min: 0 ° |
Image recording | Electron dose: 13 e/Å2 / Film or detector model: GENERIC TVIPS (4k x 4k) |
Image scans | Num. digital images: 1500 |
Radiation wavelength | Relative weight: 1 |
-Processing
EM software |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Method: RANDOM CONICAL TILT THEN REFERENCE BASED RECONSTRUCTION Resolution: 20.5 Å / Num. of particles: 25008 / Nominal pixel size: 2.96 Å / Actual pixel size: 2.96 Å / Magnification calibration: 23A LAYERLINE OF TMV Details: INITIAL MODEL FROM RANDOM CONICAL TILT FOLLOWED BY REFERENCE BASED REFINEMENT PDB FILE 3FCS WAS SPLIT INTO 20 SUBDOMAINS. THESE SUBDOMAINS WERE MANUALLY FITTED INTO THE EM VOLUME SUBMISSION ...Details: INITIAL MODEL FROM RANDOM CONICAL TILT FOLLOWED BY REFERENCE BASED REFINEMENT PDB FILE 3FCS WAS SPLIT INTO 20 SUBDOMAINS. THESE SUBDOMAINS WERE MANUALLY FITTED INTO THE EM VOLUME SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-2281. (DEPOSITION ID: 11378). Symmetry type: POINT | ||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL / Target criteria: Cross-correlation coefficient / Details: METHOD--RIGID BODY REFINEMENT PROTOCOL--X-RAY | ||||||||||||
Atomic model building | PDB-ID: 3FCS | ||||||||||||
Refinement | Highest resolution: 20.5 Å | ||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 20.5 Å
|