ArticleBlood2012
Conservative mutations in the C2 domains of factor VIII and factor V alter phospholipid binding and cofactor activity.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 41 citations in OpenAlex.
- Structural basis for membrane binding by coagulation factors V and VIII and their specificity for phosphatidylserine-containing membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell-Based Small-Molecule Screening Identifying Proteostasis Regulators Enhancing Factor VIII Missense Mutant Secretion.Biomolecules · 2025Article
- Elucidating the complex membrane binding of a protein with multiple anchoring domains using extHMMM.PLoS computational biology · 2024Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V.Current research in structural biology · 2024Article
- SAXS analysis of the intrinsic tenase complex bound to a lipid nanodisc highlights intermolecular contacts between factors VIIIa/IXa.Blood advances · 2022Article
- The role of phosphatidylserine on the membrane in immunity and blood coagulation.Biomarker research · 2022Review
- Dissection of pleiotropic effects of variants in and adjacent to F8 exon 19 and rescue of mRNA splicing and protein function.American journal of human genetics · 2021Article
- FVIII inhibitors display FV-neutralizing activity in the prothrombin time assay.Journal of thrombosis and haemostasis : JTH · 2021Article
- Procoagulant activities of skeletal and cardiac muscle myosin depend on contaminating phospholipid.Blood · 2020Article
- Rheostat positions: A new classification of protein positions relevant to pharmacogenomics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
- Recombinant Factor VIII Fc Inhibits B Cell Activation via Engagement of the FcγRIIB Receptor.Frontiers in immunology · 2020Article
- Procoagulant Phosphatidylserine-Exposing PlateletsFrontiers in cardiovascular medicine · 2020Review
- Blood coagulation factor Va's key interactive residues and regions for prothrombinase assembly and prothrombin binding.Journal of thrombosis and haemostasis : JTH · 2019Review
- Molecular mechanisms of missense mutations that generate ectopic N-glycosylation sites in coagulation factor VIII.The Biochemical journal · 2018Article
- Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking.Haematologica · 2017Article
- Missense mutations near the N-glycosylation site of the A2 domain lead to various intracellular trafficking defects in coagulation factor VIII.Scientific reports · 2017Article
- Article
- Factor VIII Interacts with the Endocytic Receptor Low-density Lipoprotein Receptor-related Protein 1 via an Extended Surface Comprising "Hot-Spot" Lysine Residues.The Journal of biological chemistry · 2015Article
- Article
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5 authors at 4 institutions in 1 country.
Funding
Abstract
Factor VIII and factor V share structural homology and bind to phospholipid membranes via tandem, lectin-like C domains. Their respective C2 domains bind via 2 pairs of hydrophobic amino acids and an amphipathic cluster. In contrast, the factor V-like, homologous subunit (Pt-FV) of a prothrombin activator from Pseudonaja textilis venom is reported to function without membrane binding. We hypothesized that the distinct membrane-interactive amino acids of these proteins contribute to the differing membrane-dependent properties. We prepared mutants in which the C2 domain hydrophobic amino acid pairs were changed to the homologous residues of the other protein and a factor V mutant with 5 amino acids changed to those from Pt-FV (FV(MTTS/Y)). Factor VIII mutants were active on additional membrane sites and had altered apparent affinities for factor X. Some factor V mutants, including FV(MTTS/Y), had increased membrane interaction and apparent membrane-independent activity that was the result of phospholipid retained during purification. Phospholipid-free FV(MTTS/Y) showed increased activity, particularly a 10-fold increase in activity on membranes lacking phosphatidylserine. The reduced phosphatidylserine requirement correlated to increased activity on resting and stimulated platelets. We hypothesize that altered membrane binding contributes to toxicity of Pt-FV.
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