Dynamic character of the complex of human blood coagulation factor VIIa with the extracellular domain of human tissue factor: a normal mode analysis

As an attempt to investigate the dynamic interactions between plasma serine protease, coagulation factor VIIa (VIIa) and its cofactor, tissue factor ( TF), we performed normal mode analysis (NMA) of the complex of VIIa with so luble TF (the extracellular part of TF; sTF). We compared fluctuations of C a atoms of VIIa or sTF derived from NMA in the VIIa-sTF complex with those of VIIa or sTF in an uncomplexed condition, The atomic fluctuations of the Ca atoms of sTF complexed with VIIa did not significantly differ from those of sTF without VIIa. In contrast, the atomic fluctuations of VIIa complexe d with sTF were much smaller than those of VIIa without sTF, These results suggest that domain motions of VIIa molecule alone are markedly dampened in the VIIa-sTF complex and that the sTF molecule is relatively more rigid th an the VIIa molecule. This map indicate functions of TF as a cofactor. (C) 1999 Federation of European Biochemical Societies.