C3konvertase

C3 konvertase is the proteolytic enzyme complex in the complement system that cleaves the central protein C3 into C3a and C3b, amplifying the immune response and promoting opsonization and inflammation. There are two main forms of C3 konvertase that arise from different activation pathways: the classical/lectin pathway C4b2a, and the alternative pathway C3bBb.

In the classical and lectin pathways, activation begins with recognition of a target surface. C1 complex (classical) or MASPs (lectin) cleaves C4 to C4a and C4b, and C2 to C2a. C4b bound on the surface associates with C2a to form C4b2a, the C3 konvertase. This complex cleaves C3 into C3a and C3b. When C3b binds to the C4b2a complex, a C5 konvertase is formed (C4b2a3b), which then cleaves C5 into C5a and C5b, advancing the terminal pathway.

In the alternative pathway, spontaneous hydrolysis of C3 produces C3(H2O), which binds factor B and is cleaved by factor D to form C3(H2O)Bb, an initial C3 konvertase. The presence of properdin stabilizes this complex, increasing its activity. C3b generated by this konvertase can bind to factor B and form the more stable C3bBb, another C3 konvertase that amplifies C3 cleavage. C3bBb can associate with additional C3b to become a C5 konvertase (C3bBb3b).

Regulation of C3 konvertases is critical and is achieved by decay-accelerating factors (such as DAF/CD55 and CR1/CD35) and by regulatory proteins like factor H and factor I, which limit convertase formation or promote their inactivation. Properdin can enhance the stability of the C3 konvertase in the alternative pathway. Dysregulation of C3 konvertases is linked to susceptibility to infections and inflammatory diseases.