1996 Fiscal Year Final Research Report Summary
Molecular bilogical studies on the assembly of the anticoagulant protein C pathway-Strucure-function relationship of the functional domains in the related molecules.
| Project/Area Number |
07458151
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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, 医学部, 助手 (00242959)
TAKEYA Hiroyuki Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (60222105)
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| Project Period (FY) |
1995 – 1996
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| Keywords | protein C pathway / protein C / protein S / thrombomodulin / factor V / prothrombin / prothrombinase complex / molecular interaction |
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| Research Abstract |
The anticoagulant protein C pathway is one of the most important systems to maintain the vascular blood fluidity. The aim of this project is to clarify the structure-function relationship of the molecules assembling in the protein C pathway to understand the molecular mechanism of this pathway. Here we studied the following three subjects : (1) Molecular mechanism of the dysfunction of protein S-Tokushima (Lys^<155>*Glu) for the regulation of the blood coagulation system. The results obtained suggest that the dysfunction of protein S-Tokushima occurs because it fails to interact with activated protein C (APC), factor Xa and prothrombin. The molecular interactions between these proteins are required for the expression of the APC cofactor activity and for the inhibition of the prothrombinase complex activity. (2) The importance of the Gla^<26> residue of protein C in expression of the anticoagulant activity of protein C on the phospholipid membrane. The results obtained suggest that Gla^<26>-dependent conformation is required for the binding of protein C and APC to phospholipids, thrombomodulin and the surface of endothelial cell protein C/APC receptor, but not to protein S and factor Va. (3) The role of the kringle domains of prothrombin during the assembly of the prothrombinase complex which efficiently produces thrombin, a physiological activator of protein C.The results obtained suggest that the kringle 2 domain interacts with factor Xa and that both kringle 1 and 2 domains of prothrombin interact with factor Va during the assembly of the prothrombinase complex. These findings may highlight the molecular mechanism of the anticoagulant protein C pathway.
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