NH2-TERMINAL CALCIUM-BINDING DOMAIN OF HUMAN-COMPLEMENT CL-BARS MEDIATES THE INTERACTION OF CL-BARR WITH CLQ

The assembly of C1, the first component of human complement, involves interactions between various domains of each of its three subcomponents, Clq, Clr, and Cls. The isolation, assignment of function, and structural characterization of the individual domains of Clr and Cls are critical for a thorough understanding of this complex assembly. The present study describes a 27-kDa plasmin-generated fragment derived from the NH2-terminal half of the heavy A chain of Cls, the activated form of Cls. This fragment, Cls-a, was shown in the presence of Ca2+ to mimic the ability of whole Cls to self-associate, bind to Clr, and facilitate the binding of Clr to Clq. These results directly prove that the Ca2+-binding sites of Cls as well as all of the determinants necessary for binding of Cls to Clr and Clq are located in the NH2-terminal 27-kDa α region of the A chain. © 1990, American Chemical Society. All rights reserved.