Domain structure and associated functions of subcomponents C1r and C1s of the first component of human complement.

Abstract

The serine protease subcomponents of the activated form of human complement C.hivin.1, C.hivin.1r and C.hivin.1s, were observed by EM after the native proteins and their limited proteolysis products, obtained from autolytic cleavage (C.hivin.1r) or from incubation with plasmin (C.hivin.1s) were rotary shadowed. At the monomeric level, both C.hivin.1r and C.hivin.1s comprised 2 globular domains, a smaller interaction domain (corresponding to the NH2-terminal half of the A chain, .alpha., and responsible for Ca binding and C.hivin.1r-C.hivin.1s interaction) and a larger catalytic domain (corresponding to the COOH-terminal part of the A chain, .gamma., disulfide-linked to the B chain and bearing the serine protease active site). The 2 globular domains are linked by a connecting strand, .beta.. The (C.hivin.1r)2 dimer appeared as a "croissant"-like association, where the 2 monomers interact through their catalytic domains. On the basis of the domain structure of C.hivin.1r and C.hivin.1s, a model of the Ca-dependent C.hivin.1s dimer is proposed, in which the 2 monomers interact through their NH2-terminal interaction domains; in the same way, a model of the C.hivin.1s-(C.hivin.1r)2-C.hivin.1s catalytic subunit of C.hivin.1 is presented, in which (C.hivin.1r)2 forms a core, its distal interaction domains interacting with the corresponding domains on C.hivin.1s.