C5Konvertase

C5 konvertase is a proteolytic enzyme complex in the mammalian complement system that cleaves the complement protein C5 into C5a and C5b. This step links the initial activation of the cascade to the terminal sequence that disrupts target cell membranes.

Formation and forms

There are two main forms of C5 konvertase corresponding to the two activating pathways. In the classical and lectin pathways, the C5 konvertase is formed when the C3 convertase C4b2a acquires an additional C3b, resulting in C4b2a3b. In the alternative pathway, the C3 convertase C3bBb gains another C3b to form C3b2Bb, which functions as the C5 konvertase. The C5 konvertases cleave C5 into C5a, a potent anaphylatoxin and chemoattractant, and C5b, which initiates the assembly of the membrane attack complex (MAC).

Function and downstream effects

C5a serves as an inflammatory mediator that recruits and activates leukocytes. C5b begins the formation of the MAC by sequential binding of C6, C7, C8, and multiple C9 molecules, creating pores in target membranes and potentially causing cell lysis. The activity of C5 konvertase is tightly regulated by various complement control proteins to limit tissue damage and prevent uncontrolled amplification.

Clinical relevance

Dysregulation or overactivation of the C5 konvertase can contribute to inflammatory and autoimmune conditions. Therapeutic approaches such as C5 inhibitors (for example, eculizumab) aim to prevent C5 cleavage, thereby reducing MAC formation and downstream inflammation. Deficiencies or dysfunctions in the pathway can increase susceptibility to certain infections, notably by Neisseria species.