Complement C5 convertase (C5 convertase)

Complement C5 convertase is a transient serine protease complex in the complement cascade that specifically cleaves complement protein C5 into C5a and C5b fragments. C5a acts as an anaphylatoxin to promote inflammation and immune cell recruitment, while C5b initiates assembly of the membrane attack complex (MAC), a pore-forming structure that lyses pathogens and altered host cells. It exists in classical/lectin pathway forms (C4bC2aC3b, with C2a as the catalytic subunit containing the Ser-His-Asp triad) and alternative pathway forms (C3bBbC3b, with Bb catalytic), requiring surface-bound C3b clusters for C5 specificity after initial C3 processing. The enzyme's instability (half-life 1-3 minutes) is regulated by inhibitors like factor H, C4BP, and factor I, which accelerate decay or promote subunit degradation. Dysregulated C5 convertase activity contributes to inflammatory and thrombotic diseases like atypical hemolytic uremic syndrome, where reduced inhibition (e.g., FHR1 deficiency) enhances MAC formation and endothelial damage. Therapeutically, targeting downstream C5 cleavage with monoclonal antibodies like eculizumab blocks convertase-generated products, treating paroxysmal nocturnal hemoglobinuria and atypical HUS but raising infection risks from impaired MAC. Structural insights reveal how C3b deposition shifts substrate specificity >1000-fold toward C5, enabling amplification on pathogen surfaces.

Other names

C3/C5 convertaseclassical pathway C5 convertase (C4b2a3b or C4bC2aC3b)alternative pathway C5 convertase (C3bBbC3b)C4b2b3b

Inhibition of C5 cleavage to prevent C5a production and C5b-initiated MAC assembly; Decay acceleration of convertase complexes; Cofactor activity for factor I-mediated degradation of C3b/C4b subunits