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Related Experiment Videos

Sequential coagulation factor VIIa domain binding to tissue factor.

Maria Osterlund1, Egon Persson, Uno Carlsson

  • 1IFM-Department of Chemistry, Linköping University, SE-581 83 Linkoping, Sweden.

Biochemical and Biophysical Research Communications
|October 21, 2005
PubMed
Summary

Vessel wall tissue factor (TF) initiates blood coagulation by binding factor VIIa (FVIIa). This study reveals TF-FVIIa complex formation occurs sequentially, starting with the protease domain, detailing the TF-FVIIa docking pathway.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Hemostasis

Background:

  • Vascular damage exposes tissue factor (TF) to blood.
  • TF initiates the coagulation cascade by binding factor VIIa (FVIIa).
  • Understanding the TF-FVIIa interaction is crucial for hemostasis research.

Purpose of the Study:

  • To elucidate the docking pathway of the FVIIa-TF complex.
  • To investigate the kinetic details of FVIIa allosteric activation by TF.
  • To map the sequential binding events between TF and FVIIa domains.

Main Methods:

  • Site-directed mutagenesis of soluble TF (sTF) with cysteine substitutions.
  • Fluorescent labeling of sTF variants.
  • Stopped-flow fluorescence kinetic measurements.

Related Experiment Videos

  • Surface plasmon resonance analysis.

    • Main Results:

    • The FVIIa-TF complex forms sequentially, initiated by the FVIIa protease domain.
    • Subsequent tethering involves the TF epidermal growth factor-like domain and FVIIa Gla domain.
    • Differential binding rates of TF residues interacting with the FVIIa protease domain were observed.
    • Removal of the FVIIa Gla domain amplified differences in domain association rates.

    Conclusions:

    • The docking trajectory of FVIIa onto TF is a multi-step process.
    • Kinetic analysis provides insights into the allosteric activation mechanism of FVIIa by TF.
    • The FVIIa Gla domain plays a significant role in the kinetics of TF binding.