ArticleBlood2013
Structure of the factor VIII C2 domain in a ternary complex with 2 inhibitor antibodies reveals classical and nonclassical epitopes.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Decoding full-length factor VIII through the structural and functional lens of its B domain.Blood vessels, thrombosis & hemostasis · 2026Article
- Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII covalent states.Blood advances · 2025Article
- Atomistic Mechanism of Lipid Membrane Binding for Blood Coagulation Factor VIII with Molecular Dynamics Simulations on a Microsecond Time Scale.The journal of physical chemistry. B · 2025Article
- Biophysical characterization of blood coagulation factor VIII binding to lipid nanodiscs that mimic activated platelet surfaces.Journal of thrombosis and haemostasis : JTH · 2025Article
- Review
- Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain.Journal of thrombosis and haemostasis : JTH · 2024Article
- Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET cohort.Blood advances · 2024Article
- Translational readthrough atHaematologica · 2023Article
- Stable binding to phosphatidylserine-containing membranes requires conserved arginine residues in tandem C domains of blood coagulation factor VIII.Frontiers in molecular biosciences · 2022Article
- Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.Research and practice in thrombosis and haemostasis · 2021Review
- Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor.Blood · 2021Article
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
- Flow-Cytometry Platform for Intracellular Detection of FVIII in Blood Cells: A New Tool to Assess Gene Therapy Efficiency for Hemophilia A.Molecular therapy. Methods & clinical development · 2020Article
- The 3.2 Å structure of a bioengineered variant of blood coagulation factor VIII indicates two conformations of the C2 domain.Journal of thrombosis and haemostasis : JTH · 2020Article
- Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.Antibodies (Basel, Switzerland) · 2018Review
- Population-specific design of de-immunized protein biotherapeutics.PLoS computational biology · 2018Article
- Article
- Engineering less immunogenic and antigenic FVIII proteins.Cellular immunology · 2016Review
- Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody.Scientific reports · 2015Article
- Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors.Journal of thrombosis and haemostasis : JTH · 2015Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
The factor VIII C2 domain is a highly immunogenic domain, whereby inhibitory antibodies develop following factor VIII replacement therapy for congenital hemophilia A patients. Inhibitory antibodies also arise spontaneously in cases of acquired hemophilia A. The structural basis for molecular recognition by 2 classes of anti-C2 inhibitory antibodies that bind to factor VIII simultaneously was investigated by x-ray crystallography. The C2 domain/3E6 FAB/G99 FAB ternary complex illustrates that each antibody recognizes epitopes on opposing faces of the factor VIII C2 domain. The 3E6 epitope forms direct contacts to the C2 domain at 2 loops consisting of Glu2181-Ala2188 and Thr2202-Arg2215, whereas the G99 epitope centers on Lys2227 and also makes direct contacts with loops Gln2222-Trp2229, Leu2261-Ser2263, His2269-Val2282, and Arg2307-Gln2311. Each binding interface is highly electrostatic, with positive charge present on both C2 epitopes and complementary negative charge on each antibody. A new model of membrane association is also presented, where the 3E6 epitope faces the negatively charged membrane surface and Arg2320 is poised at the center of the binding interface. These results illustrate the potential complexities of the polyclonal anti-factor VIII immune response and further define the "classical" and "nonclassical" types of antibody inhibitors against the factor VIII C2 domain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.