+Open data
-Basic information
Entry | Database: PDB / ID: 8ty1 | |||||||||
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Title | Cryo-EM structure of coagulation factor VIII bound to NB2E9 | |||||||||
Components |
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Keywords | BLOOD CLOTTING/INHIBITOR / Coagulation / Inhibitor antibody / factor VIII / BLOOD CLOTTING-INHIBITOR complex | |||||||||
Function / homology | Function and homology information Defective F8 accelerates dissociation of the A2 domain / Defective F8 binding to the cell membrane / Defective F8 secretion / Defective F8 sulfation at Y1699 / Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation / Defective F8 binding to von Willebrand factor / blood coagulation, intrinsic pathway / Cargo concentration in the ER / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant ...Defective F8 accelerates dissociation of the A2 domain / Defective F8 binding to the cell membrane / Defective F8 secretion / Defective F8 sulfation at Y1699 / Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation / Defective F8 binding to von Willebrand factor / blood coagulation, intrinsic pathway / Cargo concentration in the ER / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / COPII-mediated vesicle transport / COPII-coated ER to Golgi transport vesicle / Defective F8 cleavage by thrombin / Common Pathway of Fibrin Clot Formation / Intrinsic Pathway of Fibrin Clot Formation / endoplasmic reticulum-Golgi intermediate compartment membrane / platelet alpha granule lumen / acute-phase response / Golgi lumen / blood coagulation / Platelet degranulation / oxidoreductase activity / copper ion binding / endoplasmic reticulum lumen / extracellular space / extracellular region / plasma membrane Similarity search - Function | |||||||||
Biological species | Sus scrofa (pig) Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.46 Å | |||||||||
Authors | Childers, K.C. / Spiegel, P.C. | |||||||||
Funding support | United States, 2items
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Citation | Journal: To Be Published Title: Structural basis for inhibition of coagulation factor VIII reveals a shared immunogenic hot-spot on the C1 domain Authors: Childers, K.C. / Vaughan, J. / McGill, J. / Davulcu, O. / Lollar, P. / Doering, C.B. / Coxon, C.H. / Spiegel, P.C. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ty1.cif.gz | 353.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ty1.ent.gz | 277 KB | Display | PDB format |
PDBx/mmJSON format | 8ty1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ty1_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8ty1_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8ty1_validation.xml.gz | 67.3 KB | Display | |
Data in CIF | 8ty1_validation.cif.gz | 97.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ty/8ty1 ftp://data.pdbj.org/pub/pdb/validation_reports/ty/8ty1 | HTTPS FTP |
-Related structure data
Related structure data | 41710MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 168287.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Sus scrofa (pig), (gene. exp.) Homo sapiens (human) Gene: F8, F8, F8C, F8, CF8 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P12263, UniProt: P00451 | ||
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#2: Antibody | Mass: 23513.164 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) | ||
#3: Protein | Mass: 25373.285 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) | ||
#4: Polysaccharide | Source method: isolated from a genetically manipulated source Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Coagulation factor VIII bound to NB2E9 / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | |||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Cricetulus griseus (Chinese hamster) | |||||||||||||||
Buffer solution | pH: 7.4 / Details: 20 mM HEPES (pH 7.4) and 150 mM NaCl | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Specimen support | Grid mesh size: 400 divisions/in. | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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 defocus max: 2700 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.46 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 94935 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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