Interaction of human protein Z with thrombin: evaluation of the species difference in the interaction between bovine and human protein Z and thrombin.

Protein Z is a vitamin K-dependent protein of unknown function present in normal human and bovine plasma. Binding and kinetic studies showed that bovine protein Z interacts with bovine thrombin with a dissociation constant of 0.11 microM in a Ca(2+)-independent fashion and that thrombin becomes associated with phospholipid vesicles in the presence of protein Z but not in its absence (Hogg, P. J. and Stenflo, J. (1991) J. Biol. Chem., in press). In the present study the interaction of human protein Z with human thrombin and the influence of human protein Z on the association of thrombin with phospholipid vesicles was evaluated. In contrast to bovine protein Z, human protein Z bound human DIP-thrombin with a 20-fold weaker affinity at 1.5 mM Ca2+ and in a Ca(2+)-dependent fashion. Human protein Z was also less effective than bovine protein Z in promoting the association of thrombin with phospholipid vesicles. Also, bovine protein Z cleaved by thrombin at Arg-365 bound DIP-thrombin with a 10-fold weaker affinity than did native bovine protein Z. The data suggest that the species difference in the interaction between protein Z and thrombin can be explained by a difference in the COOH-terminal region of bovine protein Z versus human protein Z.