Complement C6

The complement system, functioning as a ‘complementation’ of the immune system, enhances the ability of antibody-mediated cytotoxicity and phagocyte clearance of microorganisms and damaged cells through the formation of membrane attack complex (MAC). Complement C6 (C6) is one of the composed proteins of the MAC on the surface of pathogen cell membranes. Human C6 is a 934-amino acid glycoprotein composed of a single polypeptide chain, folding as nine auxiliary/regulatory domains complementing the MAC perforin core. C6 is the longest protein, as well as an essential constituent of the MAC. During the complement activation, the alpha chain of C5 is cleaved by C5 convertase releasing C5a and C5b. C5b is unstable and remains bound to the convertase complex for a short time until it binds to a C6 in the surrounding fluid to form C5b-6 complex. The C5b-6 complex can further bind complement components C7, C8, and C9, forming the MAC.

The current role of C6 is to participate in the formation of MAC, which plays critical functions in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDCC). C6 deficiency is a rare autosomal recessive disorder. People with C6 deficiency are prone to bacterial infection (neisserial infections) and immunodeficiency due to a late component of complement deficiency.

Fig.1 Crystal structure and domain organization of C6. (Aleshin, 2012)

Reference

1. Aleshin, A.E.; et al. Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC). The Journal of Biological Chemistry. 2012, 287(13): 10210-10222.