| Project/Area Number |
05454622
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Structural biochemistry
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| Research Institution | Mie University |
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Principal Investigator |
SUZUKI Koji Mie University, Faculty of Medicine, Professor., 医学部, 教授 (70077808)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Tatsuya Mie University, Faculty of Medicine, Assistant Professor., 医学部, 助手 (00242959)
TAKEYA Hiroyuki Mie University, Faculty of Medicine, Assistant Professor., 医学部, 助手 (60222105)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1993: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Anticoagulant protein C pathway / Thrombomodulin / Protein C / Protein S / Factor X / Functional domain / EGF domain / 組換え蛋白質 / 分子間相互作用 / トロンビン / EGF様ドメイン / 血管内皮細胞 / ホモシステイン / 遺伝子発現機構 |
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| Research Abstract |
The blood fluidity in the vessel is maintained by the activation of several anticoagulant systems on the surface of intravascule, such as anticoagulant protein C pathway system and antithrombin III-heparin system.Hereditary abnormal patients, who are lacking antithrombotic factor or have abnormal molecule, are often suffered from the thrombotic diseases. Thus it is very important for diagnosis and medical treatments to study the genetic analysis and the analysis on the structure-function relationship of the normal and abnormal factors (proteins) in the anticoagulant systems. In this study, we analyzed the structure-function relationship of several factors ; thrombomodulin, protein C and protein S,which are major components in the protein C pathway. In which, a region containing the fourth to the sixth domains of the six epidermal growth factor (EGF) domains in thrombomodulin was found to serve the binding sites for thrombin and protein C during the activation of protein C by thrombin complexed with thrombomodulin. We also found that the second domain of the four EGF domains of protein S plays a crucial role as a binding site of activated protein C in the expression of the cofactor activity for activated protein C.These results suggest that the functional domains play roles in the interactions with the target proteins in the antithrombotic system.
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