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Yorodumi- PDB-9td2: Integrin AlphaIIbBeta3 bound to Fab of the anti-HPA-1a antibody 26.4 -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9td2 | ||||||||||||||||||||||||||||||||||||||||||
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| Title | Integrin AlphaIIbBeta3 bound to Fab of the anti-HPA-1a antibody 26.4 | ||||||||||||||||||||||||||||||||||||||||||
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Keywords | CELL ADHESION / Human Platelet Antigen / FNAIT / alloantibody / cryo-EM | ||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationregulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / tube development / alpha9-beta1 integrin-ADAM8 complex / response to platelet-derived growth factor / integrin alphaIIb-beta3 complex / regulation of postsynaptic neurotransmitter receptor diffusion trapping / maintenance of postsynaptic specialization structure / alphav-beta3 integrin-vitronectin complex / platelet alpha granule membrane ...regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / tube development / alpha9-beta1 integrin-ADAM8 complex / response to platelet-derived growth factor / integrin alphaIIb-beta3 complex / regulation of postsynaptic neurotransmitter receptor diffusion trapping / maintenance of postsynaptic specialization structure / alphav-beta3 integrin-vitronectin complex / platelet alpha granule membrane / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / positive regulation of glomerular mesangial cell proliferation / smooth muscle cell migration / alphav-beta3 integrin-PKCalpha complex / fibrinogen binding / positive regulation of leukocyte migration / alphav-beta3 integrin-HMGB1 complex / negative regulation of lipid transport / vascular endothelial growth factor receptor 2 binding / angiogenesis involved in wound healing / positive regulation of vascular endothelial growth factor signaling pathway / regulation of release of sequestered calcium ion into cytosol / Elastic fibre formation / mesodermal cell differentiation / positive regulation of bone resorption / alphav-beta3 integrin-IGF-1-IGF1R complex / platelet-derived growth factor receptor binding / cell-cell adhesion mediated by integrin / filopodium membrane / extracellular matrix binding / positive regulation of fibroblast migration / positive regulation of cell adhesion mediated by integrin / positive regulation of vascular endothelial growth factor receptor signaling pathway / apolipoprotein A-I-mediated signaling pathway / regulation of bone resorption / negative regulation of low-density lipoprotein particle clearance / apoptotic cell clearance / wound healing, spreading of epidermal cells / positive regulation of smooth muscle cell migration / integrin complex / glycinergic synapse / Molecules associated with elastic fibres / heterotypic cell-cell adhesion / cell adhesion mediated by integrin / positive regulation of osteoblast proliferation / negative chemotaxis / regulation of postsynaptic neurotransmitter receptor internalization / cellular response to insulin-like growth factor stimulus / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / Syndecan interactions / p130Cas linkage to MAPK signaling for integrins / cell-substrate adhesion / protein disulfide isomerase activity / microvillus membrane / PECAM1 interactions / GRB2:SOS provides linkage to MAPK signaling for Integrins / negative regulation of endothelial cell apoptotic process / TGF-beta receptor signaling activates SMADs / Fibrin formation / fibronectin binding / lamellipodium membrane / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / Integrin cell surface interactions / ECM proteoglycans / substrate adhesion-dependent cell spreading / positive regulation of T cell migration / cell-matrix adhesion / embryo implantation / coreceptor activity / Integrin signaling / positive regulation of endothelial cell proliferation / cell adhesion molecule binding / positive regulation of endothelial cell migration / positive regulation of smooth muscle cell proliferation / integrin-mediated signaling pathway / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / response to activity / regulation of actin cytoskeleton organization / protein kinase C binding / wound healing / Signal transduction by L1 / cellular response to xenobiotic stimulus / virus receptor activity / cell-cell adhesion / platelet activation / Signaling by high-kinase activity BRAF mutants / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / MAP2K and MAPK activation / VEGFA-VEGFR2 Pathway / platelet aggregation / integrin binding / blood coagulation / cellular response to mechanical stimulus / ruffle membrane / positive regulation of angiogenesis / angiogenesis / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.64 Å | ||||||||||||||||||||||||||||||||||||||||||
Authors | de Pereda, J.M. / Stam, W. / Gragera, M. / van der Meer, F. / Chichon, F.J. / Zarkadas, E. / van der Schoot, E. / Vidarsson, G. / Takagi, J. / Margadant, C. | ||||||||||||||||||||||||||||||||||||||||||
| Funding support | Netherlands, Spain, European Union, 6items
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Citation | Journal: Sci Adv / Year: 2026Title: High-resolution cryo-EM structure of integrin αIIbβ3 bound to disease-causing maternal HPA-1a antibody that blocks integrin activation. Authors: José M de Pereda / Wendy Stam / Marcos Gragera / Femke van der Meer / Francisco J Chichón / Eleftherios Zarkadas / Ellen van der Schoot / Gestur Vidarsson / Junichi Takagi / Coert Margadant / ![]() Abstract: Integrins promote immunity, embryonic development, wound healing, and hemostasis, and are activated by 'bent/closed' to 'extended/open' conformational changes. Integrin αIIbβ3, being crucial for ...Integrins promote immunity, embryonic development, wound healing, and hemostasis, and are activated by 'bent/closed' to 'extended/open' conformational changes. Integrin αIIbβ3, being crucial for platelet activation and aggregation, is a therapeutic target for bleeding disorders and thrombosis. Human Platelet Antigen-1a (HPA-1a) on β3 is recognized by pregnancy-associated maternal alloantibodies, potentially causing fetal/neonatal alloimmune thrombocytopenia (FNAIT) and even intracranial hemorrhage or perinatal death. We report the structure of an anti-HPA-1a antibody fragment (Fab 26.4) in complex with integrin αIIbβ3 at high resolution by cryo-electron microscopy. Fab 26.4 binding locks αIIbβ3 in the inactive, bent/closed conformation, is incompatible with integrin extension, and inhibits αIIbβ3-dependent fibrinogen binding and platelet aggregation. Thus, anti-HPA-1a antibodies directly impair integrin activation by preventing required conformational changes. These insights will improve FNAIT diagnostics and treatment, and spark the development of novel allosteric inhibitors against β3 integrins for future therapeutic applications. | ||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9td2.cif.gz | 619.7 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9td2.ent.gz | 505.6 KB | Display | PDB format |
| PDBx/mmJSON format | 9td2.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/td/9td2 ftp://data.pdbj.org/pub/pdb/validation_reports/td/9td2 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 55800MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
| Experimental dataset #1 | Data reference: 10.15151/ESRF-ES-2152500036 / Data set type: other 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: 108456.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGA2B, GP2B, ITGAB / Production host: ![]() |
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| #2: Protein | Mass: 81402.023 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGB3, GP3A / Production host: ![]() |
-Antibody , 2 types, 2 molecules HL
| #3: Antibody | Mass: 26033.857 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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| #4: Antibody | Mass: 23441.012 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
-Sugars , 4 types, 7 molecules 
| #5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-alpha-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: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Sugar | |
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-Non-polymers , 3 types, 16 molecules 




| #8: Chemical | ChemComp-CA / #10: Chemical | ChemComp-MG / | #11: Water | ChemComp-HOH / | |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-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: Complex of integrin aIIbb3 ectodomains bound to the Fab 26.4 Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | |||||||||||||||||||||||||
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| Molecular weight | Value: 0.24 MDa / Experimental value: NO | |||||||||||||||||||||||||
| Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||||||||||||
| Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||
| Buffer solution | pH: 7.5 Details: 50 mM Tris-HCl, 150 mM NaCl, 1 mM CaCl2, 1 mM MgCl2, pH 7.5 | |||||||||||||||||||||||||
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| Specimen | Conc.: 0.13 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
| Specimen support | Details: 25 mA / Grid material: COPPER/RHODIUM / Grid type: Quantifoil R0.6/1 | |||||||||||||||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 94 % / Chamber temperature: 277 K / Details: blotting time 3 sec, blot force 3 |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm |
| Image recording | Average exposure time: 2.93 sec. / Electron dose: 41.57 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) |
| EM imaging optics | Energyfilter name: TFS Selectris X / Energyfilter slit width: 10 eV |
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Processing
| EM software |
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 6717934 | ||||||||||||||||||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.64 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 84349 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
| Atomic model building | Protocol: RIGID BODY FIT / Space: REAL Details: Initial rigid body fitting of individual domains was done using Coot | ||||||||||||||||||||||||||||||||||||||||
| Atomic model building | 3D fitting-ID: 1
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| Refinement | Highest resolution: 2.64 Å / Cross valid method: NONE Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||||||||||||||||||
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About Yorodumi



Homo sapiens (human)
Netherlands,
Spain, European Union, 6items
Citation


PDBj
















FIELD EMISSION GUN
