Amino-terminal calcium-binding domain of human complement C1.hivin.s mediates the interaction of C1.hivin.r with C1q

Abstract

The assembly of C1, the first component of human complement, involves interactions between various domains of each of its three subcomponents, C1q, C1r, and C1s. The isolation, assignment of function, and structural characterization of the individual domains of C1r and C1s are critical for a thorough understanding of this complex assembly. The present study described a 27-kDa plasmin-generated fragment derived from the NH2-terminal half of the heavy-A chain of C1 .ovrhdot.s, the activated form of C1s. This fragment, C1 .hivin.s-.alpha., was shown in the presence of Ca2+ to mimic the ability of whole C1 .hivin.s to self-associate, bind to C1 .hivin.r and facilitate the binding of C1.hivin.r to C1q. These results directly prove that the Ca2+-binding sites of C1 .hivin.s as well as all of the determinants necessary for binding of C1 .hivin.s to C1 .hivin.r and C1q are located in the NH2-terminal 27-kDa .alpha. region of the A chain.