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Open data
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Basic information
Entry | Database: PDB / ID: 6v4p | ||||||||||||
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Title | Structure of the integrin AlphaIIbBeta3-Abciximab complex | ||||||||||||
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![]() | Cell Adhesion/Immune System / Integrin / Abciximab / BLOOD CLOTTING / Cell Adhesion-Immune System complex | ||||||||||||
Function / homology | ![]() 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 / 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 ...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 / 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 / maintenance of postsynaptic specialization structure / fibrinogen binding / alphav-beta3 integrin-HMGB1 complex / blood coagulation, fibrin clot formation / negative regulation of lipid transport / vascular endothelial growth factor receptor 2 binding / glycinergic synapse / negative regulation of low-density lipoprotein receptor activity / regulation of release of sequestered calcium ion into cytosol / angiogenesis involved in wound healing / Elastic fibre formation / 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 / wound healing, spreading of epidermal cells / positive regulation of cell adhesion mediated by integrin / heterotypic cell-cell adhesion / integrin complex / Molecules associated with elastic fibres / positive regulation of leukocyte migration / positive regulation of cell-matrix adhesion / cellular response to insulin-like growth factor stimulus / smooth muscle cell migration / microvillus membrane / cell adhesion mediated by integrin / negative chemotaxis / Syndecan interactions / p130Cas linkage to MAPK signaling for integrins / activation of protein kinase activity / cellular response to platelet-derived growth factor stimulus / protein disulfide isomerase activity / cell-substrate adhesion / 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 / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / platelet-derived growth factor receptor signaling pathway / fibronectin binding / ECM proteoglycans / positive regulation of T cell migration / positive regulation of bone resorption / Integrin cell surface interactions / coreceptor activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / 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 / cell-matrix adhesion / response to activity / Signal transduction by L1 / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / protein kinase C binding / positive regulation of smooth muscle cell proliferation / Signaling by high-kinase activity BRAF mutants / wound healing / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / MAP2K and MAPK activation / platelet activation / ruffle membrane / platelet aggregation / VEGFA-VEGFR2 Pathway / cell-cell adhesion / cellular response to mechanical stimulus / positive regulation of angiogenesis / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / regulation of protein localization Similarity search - Function | ||||||||||||
Biological species | ![]() synthetic construct (others) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
![]() | Nesic, D. / Zhang, Y. / Spasic, A. / Li, J. / Provasi, D. / Filizola, M. / Walz, T. / Coller, B.S. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex. Authors: Dragana Nešić / Yixiao Zhang / Aleksandar Spasic / Jihong Li / Davide Provasi / Marta Filizola / Thomas Walz / Barry S Coller Abstract: OBJECTIVE: The αIIbβ3 antagonist antiplatelet drug abciximab is the chimeric antigen-binding fragment comprising the variable regions of murine monoclonal antibody 7E3 and the constant domains of ...OBJECTIVE: The αIIbβ3 antagonist antiplatelet drug abciximab is the chimeric antigen-binding fragment comprising the variable regions of murine monoclonal antibody 7E3 and the constant domains of human IgG1 and light chain κ. Previous mutagenesis studies suggested that abciximab binds to the β3 C177-C184 specificity-determining loop (SDL) and Trp129 on the adjacent β1-α1 helix. These studies could not, however, assess whether 7E3 or abciximab prevents fibrinogen binding by steric interference, disruption of either the αIIbβ3-binding pocket for fibrinogen or the β3 SDL (which is not part of the binding pocket but affects fibrinogen binding), or some combination of these effects. To address this gap, we used cryo-electron microscopy to determine the structure of the αIIbβ3-abciximab complex at 2.8 Å resolution. Approach and Results: The interacting surface of abciximab is comprised of residues from all 3 complementarity-determining regions of both the light and heavy chains, with high representation of aromatic residues. Binding is primarily to the β3 SDL and neighboring residues, the β1-α1 helix, and β3 residues Ser211, Val212 and Met335. Unexpectedly, the structure also indicated several interactions with αIIb. As judged by the cryo-electron microscopy model, molecular-dynamics simulations, and mutagenesis, the binding of abciximab does not appear to rely on the interaction with the αIIb residues and does not result in disruption of the fibrinogen-binding pocket; it does, however, compress and reduce the flexibility of the SDL. CONCLUSIONS: We deduce that abciximab prevents ligand binding by steric interference, with a potential contribution via displacement of the SDL and limitation of the flexibility of the SDL residues. | ||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 243.7 KB | Display | ![]() |
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PDB format | ![]() | 187.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 677.9 KB | Display | ![]() |
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Full document | ![]() | 695.8 KB | Display | |
Data in XML | ![]() | 37.8 KB | Display | |
Data in CIF | ![]() | 58.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 21044MC M: map data used to model this data 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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Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 104894.438 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 75974.828 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Antibody , 2 types, 2 molecules CD
#3: Antibody | Mass: 24161.119 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() |
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#4: Antibody | Mass: 23501.986 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() |
-Non-polymers , 2 types, 7 molecules ![](data/chem/img/CA.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/MG.gif)
#5: Chemical | ChemComp-CA / #6: Chemical | ChemComp-MG / | |
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-Details
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 |
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Sample preparation
Component | Name: Integrin AlphaIIbBeta3-Abciximab Complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: NITROGEN |
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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 |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1161396 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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