Complement component 8 and Complement component 9 (C8 and C9)

Complement components C8 and C9 are the final protein subunits that participate in assembly of the membrane attack complex (MAC), a key effector of the terminal complement pathway in the innate immune system[7][9]. C8 is a heterotrimer of α, β, and γ subunits; it anchors the complex to the target cell membrane and initiates pore formation by allowing subsequent C9 monomers to bind and oligomerize[1][3][5][8]. C9 then polymerizes to form a large β-barrel pore that disrupts membrane integrity, causing cell lysis and death of pathogens[5][7][8]. Deficiencies in C8 or C9 lead to susceptibility to Neisseria infections, while over-activation is implicated in autoimmune and inflammatory tissue damage. Some therapies indirectly target MAC formation (by inhibiting C5); direct targeting of C8 or C9 is still emerging[6]. CD59 is an endogenous membrane regulator that binds both C8 and C9 to block MAC assembly and prevent host cell damage[6].

Other names

Membrane attack complex proteins C8 and C9terminal complement proteins C8 and C9complement C8 and C9

Inhibition of MAC assembly by blocking C5 cleavage (prevents C5b formation and thus recruitment of C6–C9) Blockade of C9 polymerization (targeting assembly, usually with biologics such as CD59 mimetics)[6] Neutralization of complement-mediated cell lysis