THE COVALENT BINDING REACTION OF COMPLEMENT COMPONENT C3

The covalent binding of C3 to target molecules on the surfaces of path ogens is crucial in most complement-mediated activities. When C3 is ac tivated, the acyl group is transferred from the sulfhydryl of the inte rnal thioester to the hydroxyl group of the acceptor molecule; consequ ently, C3 is bound to the acceptor surface by an ester bond. It has be en determined that the binding reaction of the B isotype of human C4 u ses a two-step mechanism. Upon activation, a His residue first attacks the internal thioester to form an acyl-imidazole bond. The freed thio late anion of the Cys residue of the thioester then acts as a base to catalyze the transfer of the acyl group from the imidazole to the hydr oxyl group of the acceptor molecule. In this article, we present resul ts which indicate that this two-step reaction mechanism also occurs in C3.