FUNCTIONAL-ANALYSIS OF THE SERPIN DOMAIN OF C1 INHIBITOR

To analyze the role of the heavily glycosylated amino-terminal domain of C1 inhibitor in protease inhibitory activity, two truncated C1 inhi bitor molecules were constructed. The abilities of the recombinant tru ncated inhibitors to complex with target proteases were compared with that of the wild-type recombinant protein. One recombinant truncated m olecule consisted of amino acid residues 76 to 478 (C-serp(76)) and th e other of residues 98 to 478 (C-serp(98)). The recombinant proteins w ere each expressed in similar quantities. The thermal denaturation pro files of the two truncated proteins were similar to that of the wild-t ype protein. Identical binding of C1s, C1r, kallikrein, and beta facto r XIIa was observed with the three molecules. Furthermore, the truncat ed molecules also effectively inhibited C1 activity in hemolytic assay s. These studies therefore clearly demonstrate that the amino-terminal domain of C1 inhibitor does not influence complex formation with targ et proteases.