Complement C3 Convertase

Activation of complement is very important for protection against microbial infections, but over-activation of complement leads to host tissue damage. The complement system is activated in two ways: (1) specific recognition of target cells in the classical and lectin pathways and (2) spontaneously due to the inherent instability of complement component C3 in the alternative (AP) pathways. These pathways converge in the generation of C3 convertases, which cleave C3 into the small anaphylatoxin C3a and the large C3b, which may bind to target surfaces. In the amplification loop of the AP pathway, pro-enzyme factor B (FB) binds to surface-bound C3b and is cleaved by factor D causing an active convertase complex that is made up of C3b and the non-covalently bound protease fragment Bb (denoted C3bBb).

C3 convertases are produced in the classical and lectin pathways via C4 and C2, which are homologs of C3 and FB respectively. It is worth noting that both C3 convertases (C3bBb and C4b2a) are active only towards their natural substrate C3, and with limited activity towards the homolog C5. Besides, in the terminal complement pathway, the substrate specificity is switched from C3 to C5 after the association of one or more C3b molecules to the C3bBb or C4b2a complexes. In addition, the complement activity can be regulated via convertase assembly and disassembly, which is controlled by complement regulators.

Fig. 1 Complement convertases mediate C3 conversion.¹

Reference

1. Zwarthoff, Seline A., et al. "Functional characterization of alternative and classical pathway C3/C5 convertase activity and inhibition using purified models." Frontiers in immunology 9 (2018): 1691.