ArticleJournal of thrombosis and haemostasis : JTH2019
Hydrogen-deuterium exchange mass spectrometry highlights conformational changes induced by factor XI activation and binding of factor IX to factor XIa.
Article in Journal of thrombosis and haemostasis : JTH, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- The Light Chain Allosterically Enhances the Protease Activity of Murine Urokinase-Type Plasminogen Activator.Biochemistry · 2024Article
- Capturing the Dynamic Conformational Changes of Human Isocitrate Dehydrogenase 1 (IDH1) upon Ligand and Metal Binding Using Hydrogen-Deuterium Exchange Mass Spectrometry.Biochemistry · 2023Article
- HK is the apple of FXI's eye.Journal of thrombosis and haemostasis : JTH · 2022Article
- Nanobodies against factor XI apple 3 domain inhibit binding of factor IX and reveal a novel binding site for high molecular weight kininogen.Journal of thrombosis and haemostasis : JTH · 2022Article
- Basic science research opportunities in thrombosis and hemostasis: Communication from the SSC of the ISTH.Journal of thrombosis and haemostasis : JTH · 2022Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Analysis of 272 Genetic Variants in the Upgraded Interactive FXI Web Database Reveals New Insights into FXI Deficiency.TH open : companion journal to thrombosis and haemostasis · 2021Article
- Aprotinin Inhibits Thrombin Generation by Inhibition of the Intrinsic Pathway, but is not a Direct Thrombin Inhibitor.TH open : companion journal to thrombosis and haemostasis · 2021Article
- Role of platelets in regulating activated coagulation factor XI activity.American journal of physiology. Cell physiology · 2021Article
- Protease activity in single-chain prekallikrein.Blood · 2020Article
- Hydrogen-deuterium exchange mass spectrometry highlights conformational changes induced by factor XI activation and binding of factor IX to factor XIa.Journal of thrombosis and haemostasis : JTH · 2019Article
- Toward a better understanding of factor XI activation.Journal of thrombosis and haemostasis : JTH · 2019Article
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundFactor XI (FXI) is a zymogen in the coagulation pathway that, once activated, promotes haemostasis by activating factor IX (FIX). Substitution studies using apple domains of the homologous protein prekallikrein have identified that FIX binds to the apple 3 domain of FXI. However, the molecular changes upon activation of FXI or binding of FIX to FXIa have remained largely unresolved.
objectivesThis study aimed to gain more insight in the FXI activation mechanism by identifying the molecular differences between FXI and FXIa, and in the conformational changes in FXIa induced by binding of FIX.
methodsHydrogen-deuterium exchange mass spectrometry was performed on FXI, FXIa, and FXIa in complex with FIX.
resultsBoth activation and binding to FIX induced conformational changes at the interface between the catalytic domain and the apple domains of FXI(a)-more specifically at the loops connecting the apple domains. Moreover, introduction of FIX uniquely induced a reduction of deuterium uptake in the beginning of the apple 3 domain.
conclusionsWe propose that the conformational changes of the catalytic domain upon activation increase the accessibility to the apple 3 domain to enable FIX binding. Moreover, our HDX MS results support the location of the proposed FIX binding site at the beginning of the apple 3 domain and suggest a mediating role in FIX binding for both loops adjacent to the apple 3 domain.
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