Structures of Complement Control Proteins

Abstract

Complement is an element of innate immunity consisting of a system of approx 30 interacting plasma proteins and cell surface receptors. This system can be activated by antibody clustering (the classical pathway), binding of mannose-binding lectin (MBL) to carbohydrates in bacterial cell walls (the MBL pathway), or cleavage of C3, a plasma complement protein, and deposition of one of its fragments, C3b, on cell surfaces (the alternative pathway). Initiation of any of these pathways leads to a serial cascade of proteolysis-mediated activation of proteins in the plasma (fluid phase) and on cell surfaces (solid phase). The three initiation pathways converge on a common pathway that results in the formation of the membrane attack complex (MAC), a multiprotein pore-forming structure capable of lysing cells. Since activation through any of these pathways can occur almost instantly and without the participation of cellular elements, the complement system is an essential first line of attack against microbial infection.