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Related Experiment Videos

Late-fibrin(ogen) fragment E modulates human alpha-thrombin specificity

M C Bouton1, M Jandrot-Perrus, A Bezeaud

  • 1Laboratoire de Recherche sur l'Hémostase et la Thrombose, Faculté Xavier Bichat, Paris, France.

European Journal of Biochemistry
|July 1, 1993
PubMed
Summary

Fragment E from fibrinogen modulates alpha-thrombin activity by competitively inhibiting interactions with fibrin, platelets, and thrombomodulin. This suggests overlapping binding sites on alpha-thrombin for these molecules.

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Area of Science:

  • Biochemistry
  • Hematology
  • Enzymology

Background:

  • Fibrinogen is a key protein in blood coagulation.
  • Alpha-thrombin is a crucial enzyme in the coagulation cascade.
  • Understanding the interactions between fibrinogen and alpha-thrombin is vital for hemostasis research.

Purpose of the Study:

  • To investigate the role of fibrinogen's E domain in modulating alpha-thrombin's enzymatic activity and binding specificities.
  • To determine if fibrin-thrombin interactions influence alpha-thrombin's catalytic center.
  • To elucidate the binding interactions of alpha-thrombin with fibrin, platelets (GPIb), and thrombomodulin.

Main Methods:

  • Utilized late-fibrinogen fragment E in competition experiments.
  • Assessed modulation of alpha-thrombin's enzymatic activity on synthetic substrates.

Related Experiment Videos

  • Measured inhibition of fibrinopeptide-A cleavage.
  • Quantified inhibition of alpha-thrombin-induced serotonin release from platelets.
  • Analyzed alpha-thrombin binding to GPIb and thrombomodulin.

    • Main Results:

    • Fragment E modulated alpha-thrombin's activity on synthetic substrates, suggesting conformational changes near the catalytic site.
    • Fragment E competitively inhibited fibrinopeptide-A cleavage (Ki = 5.2 microM), indicating significant contribution of fibrin moiety to fibrinogen hydrolysis.
    • Fragment E inhibited alpha-thrombin-induced serotonin release (IC50 = 10 microM) and binding to GPIb.
    • Fragment E competitively inhibited thrombomodulin binding (Ki = 18.3 microM) but not protein C activation without thrombomodulin.

    Conclusions:

    • Fibrin-thrombin interactions, mediated by fragment E, subtly alter alpha-thrombin's conformation and activity.
    • Fragment E binding to alpha-thrombin suggests overlapping binding sites for fibrin, platelet GPIb, and thrombomodulin.
    • Protein C appears to bind to an independent site on alpha-thrombin, distinct from those interacting with fibrin, GPIb, or thrombomodulin.