Text Size:AAA

Complement MAC Gene Cluster

Complement MAC I Gene Cluster (Proteins | Antibodies | Genes | ELISA Kits)


Complement MAC Gene Cluster (Proteins | Antibodies | Genes | ELISA Kits)

C6 C7 C9

Complement MAC Gene Cluster Background

Complement component C6, C7 and C9 share not only functional similarities as members of a functional unit, the terminal complement cascade, they are also biochemically and structurally similar and share a common ancestor, which was very likely a C6-like and not a C9-like molecule. Despite gene duplications and deletions, the genes for C6, C7 and C9 remain located in the same chromosomal region (5p13) in the MAC II gene cluster (unlike the C8A and C8B genes which are located at 1p32 (MAC I).

Activation of complement triggers assembly of the membrane attack complex (MAC), a multi-protein pore that inserts into and directly lyses microbes. MAC is deployed to kill a wide range of Gram-negative bacteria. It is essential for defense against Neisseria meningitidis, with genetic deficiencies in MAC components leading to recurrent infections. Unregulated MAC formation causes host tissue damage, whereas sublytic pore concentrations trigger signal transduction pathways that activate events including proliferation.

Complement MAC Deficiency

Looking at the multiple functions of the complement MAC, it is no surprise that the MAC has been implicated in an impressive number of diseases, evident via its detection in diseased tissues or its elevated levels in the blood , and that so many different clinically relevant microorganism have adopted numerous different techniques to escape the destructive action of complement. MAC deficiency involves deficiencies of C5, C6, C7, C8, and C9. People with complement MAC deficiency are prone to Neisseria meningitidis infection. Deficiencies of the terminal cascade predispose to meningococcal infections, indicating that its cytolytic properties are of particular importance in host defence against Neisseria, for which there appears to be no sufficient back-up. Neutrophils can only provide partial protection, although they can kill meningococci when incubated in terminal complement deficient serum, and this effect increases after vaccination so that this may represent an alternative treatment option in addition to, or instead of, vigilance and antibiotic prophylaxis.

Complement Deficiency Diseases Complement System Structure Complement Activation Pathways

Complement MAC Gene Cluster References

1. Würzner R. (2003). Deficiencies of the complement MAC II gene cluster (C6, C7, C9): is subtotal C6 deficiency of particular evolutionary benefit?. Clinical & Experimental Immunology, 133(2), 156-159.
2. Serna M, et al. (2016). Structural basis of complement membrane attack complex formation. Nature communications, 7.