Coagulation factor Va is an actin filament binding and cross-linking protein.
Bovine coagulation cofactor factor Va is shown to bind to filament of skeletal muscle actin with a dissociation constant of 40-50 nM in the presence of 50 mM NaCl. At saturation, approximately one molecule of factor Va was bound for every two actin molecules. The binding of factor Va to F-actin was inhibited by increasing ionic strength, being approximately 20-fold weaker at 150 mM NaCl. Addition of factor Va dramatically increased both the low-speed sedimentation and the low-shear viscosity of actin filament solutions, indicating that factor Va cross-linkis actin filaments. Factor Va bound to actin filaments saturated with myosin. The isolated 74-kilodalton light chain of factor Va displayed actin binding and cross-linking properties indistinguishable from those of intact factor Va. The procofactor factor V bound weakly to F-actin, indicating that proteolytic activation is required to uncover the actin binding sites within the light chain domain. Actin filaments had only a slight inhibitory effect on the prothombinase activity of the factor Va-factor Xa-phospholipid complex. Since high concentrations of actin filaments can be exposed to the circulation when cells are damaged, the interaction of factor Va with actin may be of physiological relevance.
Furmaniak-Kazmierczak
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Department of Biochemistry, Queen's University, Kingston, ON, Canada.
Nesheim
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Côté
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D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003432:Cross-Linking Reagents / Q000378:metabolism*; D005165:Factor V / Q000378:metabolism; D015943:Factor Va / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D009218:Myosins / Q000378:metabolism; D009994:Osmolar Concentration; D012965:Sodium Chloride; D013925:Thromboplastin / Q000037:antagonists & inhibitors; D014461:Ultracentrifugation; D014783:Viscosity
D000199:Actins; D003432:Cross-Linking Reagents; D065427:Factor Xa Inhibitors; D012965:Sodium Chloride; D015943:Factor Va; D005165:Factor V; D000205:Actomyosin; D013925:Thromboplastin; D015951:Factor Xa; D009218:Myosins