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

FEBS Letters

Soejima, Kenji¹  Umeyama, Hideaki²  Kamiya, Kenshu³  Kurihara, Youji² 

[1] First Research Department, Chemo-Sero-Therapeutic Research Institute, Kawabe, Kyokushi-mura, Kikuchi-gun, Kumamoto 869-1298, Japan;School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan;School of Science, Kitasato University, 1-15-1 Kitasato, Sagamihara-Shi, Kanagawa 228-8555, Japan

关键词: Domain motion;    Factor VIIa;    Tissue factor;    Factor VIIa-tissue factor complex;    Normal mode analysis;    VII;    coagulation factor VII;    VIIa;    activated coagulation factor VII;    Gla;    γ-carboxyglutamic acid;    EGF;    epidermal growth factor;    TF;    tissue factor;    sTF;    soluble tissue factor;    NMA;    normal mode analysis;   

DOI  :  10.1016/S0014-5793(99)01564-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 soluble TF (the extracellular part of TF; sTF). We compared fluctuations of Cα 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 Cα atoms of sTF complexed with VIIa did not significantly differ from those of sTF without VIIa. In contrast, the atomic fluctuations of VIIa complexed 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 than the VIIa molecule. This may indicate functions of TF as a cofactor.

【 授权许可】

Unknown