Complement Component C1S

Complement Component C1: C1S Background

The complement system is made up of more than 20 different plasma proteins that are sequentially activated through the classical or alternative pathways. Activation by either pathway leads to the generation of activated C3, to the formation of a membrane-attack complex which is responsible for lysis of the target cells, and to the generation of proteolytic fragments that have anaphylatoxin activity.

The first step in the activation of the classical pathway is brought about by the interaction of the C1 complex with antibody-antigen complexes or antibody bound to the surface antigens of target cells. The C1 complex is made up of three subcomponents: C1q, a molecule of unusual structure having six collagen-like stalks coming together at one end to form a short section of fibril, and six globular heads to which the CH2 domain of immunoglobulins can bind. C1r and C1s, two similar molecules occurring in the ratio of 1:2:2 in the C1q:C1r:C1s complex, with structures similar to many of the coagulation and fibrinolytic enzymes in having zymogen structures that are converted to active proteolytic enzymes during activation. Activation of the C1 complex is still poorly understood, with little direct evidence to elucidate the interaction of the subcomponents in the complex. Initially the active form of C1r is generated by an apparently autocatalytic process and this then activates C1s, which then cleaves C2 and C4 to continue the activation process. Active forms of C1r and C1s can be distinguished from the zymogens (Mr=85000) by their two-chain structure, with the serine proteinase activity associated with the smaller (Mr=27000) C-terminal chain which is disulphide-bridged to the larger (Mr=58000) Nterminal chain. Once activated, C1r and C1s can be inhibited by forming a stoichiometric complex with C1 inhibitor, a molecule that has a typical "serpin" type of structure. C1 inhibitor is also thought to control activation of C1 while C1r and C1s are still in the zymogen form.

Complement Component C1: C1S Reference

1. MacKinnon C M, et al. (1987). Molecular cloning of cDNA for human complement component C1s. European Journal of Biochemistry, 169(3), 547-553.
2. Busby W H, et al. (2000). The complement component C1s is the protease that accounts for cleavage of insulin-like growth factor-binding protein-5 in fibroblast medium. Journal of Biological Chemistry, 275(48), 37638-37644.
3. NISSEN M H, et al. (1990). Limited proteolysis of β2‐microglobulin at Lys‐58 by complement component C1s. European Journal of Biochemistry, 189(2), 423-429.