AMINO-ACIDS 225-235 OF THE PROTEIN-C SERINE-PROTEASE DOMAIN ARE IMPORTANT FOR THE INTERACTION WITH THE THROMBIN THROMBOMODULIN COMPLEX

Protein C (PC) is a vitamin K-dependent zymogen that inactivates factors Va and Vma 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.