ArticleBlood2022
Cryo-EM structure of the prothrombin-prothrombinase complex.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Protein-protein interaction disruption as a next-generation antithrombotic strategy.Journal of thrombosis and thrombolysis · 2026Review
- 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
- Cryogenic electron microscopy and coagulation factors.Current opinion in hematology · 2026Review
- Molecular mechanism of cleavage at R271 during prothrombin activation revealed by cryo-EM.Blood · 2026Article
- Prothrombinase processivity is conferred by substrate allostery.The EMBO journal · 2026Article
- In vivo targeting of open prothrombin with the monoclonal antibody POmAb results in anticoagulation without excessive bleeding.Journal of thrombosis and haemostasis : JTH · 2026Article
- Spider venom phospholipase D toxin structure: Interfacial binding site, mechanism, activation, and head group preference.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- How to mitigate the caveat emptor burden of human and machine users of the Protein Data Bank.Acta crystallographica. Section D, Structural biology · 2026Article
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- The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Review
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- Deciphering conformational dynamics in AFM data using fast nonlinear NMA and FFT-based search with AFMFit.Communications biology · 2025Article
- Targeting hemostatic enzymes: from mechanistic insights to therapeutic frontiers.Current opinion in hematology · 2025Review
- Basic regions of factor V and tissue factor pathway inhibitor mediate heavy chain and acidic region interactions on factor V revealed by tethered chemical cleavage.Journal of thrombosis and haemostasis : JTH · 2025Article
- Article
- Reversible High-Affinity Binding of Coagulation Factor Xa to Zeolites Induces Accelerated Blood Coagulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Novel Human Anti-FV mAb as a Potential Tool for Diagnostic and Coagulation Inhibitory Approaches.International journal of molecular sciences · 2025Article
- Membrane-bound model of the ternary complex between factor VIIa/tissue factor and factor X.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
- Serious issues with cryo-EM structures of human prothrombinase.Open biology · 2025Review
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5 authors at 2 institutions in 2 countries.
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Abstract
The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where the prothrombinase complex, comprising the enzyme factor Xa (fXa), the cofactor fVa, Ca2+ and phospholipids, activates the zymogen prothrombin to the protease thrombin. The reaction entails cleavage at 2 sites, R271 and R320, generating the intermediates prethrombin 2 and meizothrombin, respectively. The molecular basis of these interactions that are central to hemostasis remains elusive. We solved 2 cryogenic electron microscopy (cryo-EM) structures of the fVa-fXa complex, 1 free on nanodiscs at 5.3-Å resolution and the other bound to prothrombin at near atomic 4.1-Å resolution. In the prothrombin-fVa-fXa complex, the Gla domains of fXa and prothrombin align on a plane with the C1 and C2 domains of fVa for interaction with membranes. Prothrombin and fXa emerge from this plane in curved conformations that bring their protease domains in contact with each other against the A2 domain of fVa. The 672ESTVMATRKMHDRLEPEDEE691 segment of the A2 domain closes on the protease domain of fXa like a lid to fix orientation of the active site. The 696YDYQNRL702 segment binds to prothrombin and establishes the pathway of activation by sequestering R271 against D697 and directing R320 toward the active site of fXa. The cryo-EM structure provides a molecular view of prothrombin activation along the meizothrombin pathway and suggests a mechanism for cleavage at the alternative R271 site. The findings advance our basic knowledge of a key step of coagulation and bear broad relevance to other interactions in the blood.
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