C3convertase

C3 convertase refers to the enzyme complexes of the complement system that cleave the complement component C3 into C3a and C3b. By generating C3b, these complexes promote opsonization of microbes and amplify the downstream complement response; C3a acts as an anaphylatoxin, contributing to inflammation.

There are two main C3 convertases in humans. In the classical and lectin pathways, the C3 convertase is C4b2a, formed when C4b binds to the activating surface and associates with the protease C2a. In the alternative pathway, the C3 convertase is C3bBb, formed when C3b binds factor B, which is cleaved by factor D to Bb. The classical/lectin pathway convertase can acquire an additional C3b to form a C5 convertase of the form C4b2a3b, capable of cleaving C5.

Regulation and stabilization of C3 convertases are essential for controlling complement activity. Factor H and Factor I regulate the alternative pathway by inactivating C3b, while C4-binding protein regulates C4b. Decay-accelerating factors such as DAF (CD55) promote dissociation of C2a from C4b and Bb from C3b, attenuating the convertases. MCP (CD46) acts as a cofactor for Factor I, and CR1 (CD35) also contributes to regulation. Properdin stabilizes the C3bBb complex on microbial surfaces, increasing its half-life. Soluble regulators such as S-protein/vitronectin can inhibit progression to the terminal pathway by preventing formation or stabilization of the C5 convertase and MAC.

Clinical relevance includes dysregulation of C3 convertases in diseases such as atypical hemolytic uremic syndrome and other complement-mediated disorders. Therapeutic approaches target various complement components to modulate C3 convertase activity and downstream effects.