Activation of the complement system occurs through three pathways, the classical pathway , the alternative pathway (Fig.1) and the lectin pathway . All of these pathways share a similar molecular
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architecture in that an initial recognition event is amplified by a succession of proteolytic enzymes in a cascade-like fashion, resulting in the generation of numerous biologically active complement activation products. One activation product of the complement system is the macromolecular membrane attack complex (MAC) , which inserts itself into target membranes, leading to the impairment of membrane function and physical destruction of targets including viruses, bacteria, parasites and tumor cells. Another activation product is C3b which attaches itself covalently to cells, immune complexes and other particles, a process called opsonization. Opsonization tags cells and particles for removal by phagocytes. Further products of proteolytic degradation of C3b (iC3b, C3dg, C3d) are recognized by specific receptors on various immune cells, and have important functions in the regulation of the adaptive immune response. Last but not least, the anaphylatoxins C3a and C5a exhibit important pro-inflammatory activities, such as degranulation of mast cells, increased vascular permeability, and chemotaxis and activation of neutrophils. Both anaphylatoxins are rapidly inactivated by the removal of a C-terminal arginine residue through the action of carboxypeptidase N. However the inactivated form of C5a, C5a-des-Arg, still exhibits its activity for neutrophils, making C5a a particularly powerful pro-inflammatory peptide (reviewed in Vogel et al., 2010, and references therein). |
 Figure 1: The classical and alternative complement pathways. (Image from Wikimedia / licensed under Creative Commons). |
Complement system impairing toxins target or mimic several complement system proteins. Only a few of them have had their activity specifically described. For example, snake venom complement C3 homologs are structural and functional analogs of complement component C3b. The snake venom serine proteinase flavoxobin independently cleaves endogenous C3 and kick-starts the complement cascade, the cobra metalloproteinase oxiagin prevents interaction of component C2 with C4b, while the cobra metalloproteinase atrase-B cleaves complement factors B, C6, C7, and C8. Most complement system impairing toxins have just been investigated for their effects on hemolytic complement activity, without having a more specific function described.
See also UniProt-keyword.