ArticleBlood2021
Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Decoding full-length factor VIII through the structural and functional lens of its B domain.Blood vessels, thrombosis & hemostasis · 2026Article
- Molecular mechanism of cleavage at R271 during prothrombin activation revealed by cryo-EM.Blood · 2026Article
- A combinatorial CAAR-T cell strategy to eliminate factor VIII inhibitors in preclinical models of hemophilia A.iScience · 2026Article
- Estimate of Numbers of Disulfide-Bonded Protein States.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII covalent states.Blood advances · 2025Article
- Article
- Biophysical characterization of blood coagulation factor VIII binding to lipid nanodiscs that mimic activated platelet surfaces.Journal of thrombosis and haemostasis : JTH · 2025Article
- 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
- The Prothrombin-Prothrombinase Interaction.Sub-cellular biochemistry · 2024Review
- Lactadherin's Multistate Binding Predicts Stable Membrane-Bound Conformations of Factors V and VIII's C Domains.Biochemistry · 2023Article
- Structure of coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor.Blood · 2023Article
- Cryo-EM structure of coagulation factor V short.Blood · 2023Article
- Cryo-EM structures of coagulation factors.Research and practice in thrombosis and haemostasis · 2022Review
- SAXS analysis of the intrinsic tenase complex bound to a lipid nanodisc highlights intermolecular contacts between factors VIIIa/IXa.Blood advances · 2022Article
- Removal of single-site N-linked glycans on factor VIII alters binding of domain-specific monoclonal antibodies.Journal of thrombosis and haemostasis : JTH · 2022Article
- Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.Research and practice in thrombosis and haemostasis · 2021Review
- Article
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies.
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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.