Complement C3 convertase (C3 convertase)

Complement C3 convertase is a critical serine protease complex in the complement system, existing as C3bBb in the alternative pathway or C4bC2b in the classical and lectin pathways, formed by C3b (or C4b) binding factor B (or C2) and cleaved by factor D (or MASP-2). It cleaves complement component C3 into C3a (an anaphylatoxin) and C3b, initiating a powerful amplification loop that deposits C3b on pathogens for opsonization, triggers inflammation, and propagates downstream to form the membrane attack complex. Structurally, the active site resides in the serine protease domain of Bb (or C2b), positioned near C3b's C345C and CUB domains via a metal-ion-dependent adhesion site (MIDAS) involving Mg2+. Dysregulation of C3 convertase activity underlies diseases like atypical hemolytic uremic syndrome and age-related macular degeneration, where overactivation damages host tissues. Therapeutic targeting focuses on inhibitors like compstatin analogs that block C3b interactions or stabilize inactive pro-convertase forms, though challenges include balancing efficacy against heightened infection susceptibility.

Other names

C3bBb (alternative pathway)C4bC2b (classical pathway)pro-convertase (C3bB)

Inhibition of convertase assembly, Stabilization of inactive complexes, Blocking C3b-factor B interaction, Decay acceleration