Amino acids 225–235 of the protein C serine‐protease domain are important for the interaction with the thrombin‐thrombomodulin complex

FEBS Letters

Vincenot, A.¹  Debost, S.¹  Aiach, M.¹  Gaussem, P.¹  Pittet, J.L.² 

[1] INSERM U428, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, 4 avenue de l'Observatorie, F-75270 Paris cedex 06, France;Société bio Mérieux, Département d'hémostase, F-69280 Marcy-l'Etoile, France

关键词: Protein C;    Activation;    Monoclonal antibody;    Thrombin-thrombomodulin complex;    PC;    protein C;    mAb;    monoclonal antibody;    APC;    activated protein C;    Ig;    immunoglobulin;   

DOI  :  10.1016/0014-5793(95)00552-K

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Protein C (PC) is a vitamin K-dependent zymogen that inactivates factors Va and VIIIa after its activation by thrombin complexed to thrombomodulin. We characterized a monoclonal antibody (mAb) against PC, whose only influence on PC functions was to inhibit PC activation by the thrombin-thrombomodulin complex. It recognized an epitope in the PC heavy chain, the conformation of which is calcium-dependent. The mAb did not recognize a natural PC variant that was not activated by the thrombin-thrombomodulin complex (mutation R229Q) and did recognize a synthetic peptide corresponding to PC amino acids 225–235 in an Elisa assay. The peptide inhibited PC activation by the thrombin-thrombomodulin complex. These data confirm that the calcium-binding loop of the serine-protease domain is involved in the interaction of PC with the thrombin-thrombomodulin complex.

【 授权许可】

Unknown