ArticleJournal of thrombosis and haemostasis : JTH2022
Characterization of interaction between blood coagulation factor VIII and LRP1 suggests dynamic binding by alternating complex contacts.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Decoding full-length factor VIII through the structural and functional lens of its B domain.Blood vessels, thrombosis & hemostasis · 2026Article
- The ligand preference of LRP1 is regulated by O-glycans.Science advances · 2026Article
- Mutations of six amino acid residues in a B domain-deleted blood coagulation factor VIII have a cumulative effect on increasing its secretion.Research and practice in thrombosis and haemostasis · 2026Article
- Exploring the Two-Way Link between Migraines and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.Thrombosis and haemostasis · 2024Article
- Revisiting Virchow's triad: exploring the cellular and molecular alterations in cerebral venous congestion.Cell & bioscience · 2024Article
- The aptamer BT200 blocks interaction of K1405-K1408 in the VWF-A1 domain with macrophage LRP1.Blood · 2024Article
- Factor VIII moiety of recombinant Factor VIII Fc fusion protein impacts Fc effector function and CD16Frontiers in immunology · 2024Article
- Plasma Clearance of Coagulation Factor VIII and Extension of Its Half-Life for the Therapy of Hemophilia A: A Critical Review of the Current State of Research and Practice.International journal of molecular sciences · 2023Review
- Characterization of interaction between blood coagulation factor VIII and LRP1 suggests dynamic binding by alternating complex contacts.Journal of thrombosis and haemostasis : JTH · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDeficiency in blood coagulation factor VIII (FVIII) results in life-threating bleeding (hemophilia A) treated by infusions of FVIII concentrates. To improve disease treatment, FVIII has been modified to increase its plasma half-life, which requires understanding mechanisms of FVIII catabolism. An important catabolic actor is hepatic low density lipoprotein receptor-related protein 1 (LRP1), which also regulates many other clinically significant processes. Previous studies showed complexity of FVIII site for binding LRP1.
objectivesTo characterize binding sites between FVIII and LRP1 and suggest a model of the interaction.
methodsA series of recombinant ligand-binding complement-type repeat (CR) fragments of LRP1 including mutated variants was generated in a baculovirus system and tested for FVIII interaction using surface plasmon resonance, tissue culture model, hydrogen-deuterium exchange mass spectrometry, and in silico.
resultsMultiple CR doublets within LRP1 clusters II and IV were identified as alternative FVIII-binding sites. These interactions follow the canonical binding mode providing major binding energy, and additional weak interactions are contributed by adjacent CR domains. A representative CR doublet was shown to have multiple contact sites on FVIII.
conclusionsFVIII and LRP1 interact via formation of multiple complex contacts involving both canonical and non-canonical binding combinations. We propose that FVIII-LRP1 interaction occurs via switching such alternative binding combinations in a dynamic mode, and that this mechanism is relevant to other ligand interactions of the low-density lipoprotein receptor family members including LRP1.
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