Complement membrane attack complex

The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector of the immune system. Antibody-mediated complement activation leads to MAC deposition on the surface of infected cells.^[1] Assembly of the MAC leads to pores that disrupt the cell membrane of target cells, leading to cell lysis and death.^[2]

The MAC is composed of the complement components C5b, C6, C7, C8 and several C9 molecules.

A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-6-7-8 complex. C5b-6-7-8 subsequently binds to C9^[3]^[4]^[5] and acts as a catalyst in the polymerization of C9.

^ Xie CB, Jane-Wit D, Pober JS (2020). "Complement Membrane Attack Complex: New Roles, Mechanisms of Action, and Therapeutic Targets". The American Journal of Pathology. 190 (6): 1138–1150. doi:10.1016/j.ajpath.2020.02.006. PMC 7280757. PMID 32194049.
^ Janeway, CA Jr; Travers P; Walport M; et al. (2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland Science. Retrieved 4 January 2018.
^ Stanley KK, Marazziti D, Eggertsen G, Fey GH (1988). "Relationships between the gene and protein structure in human complement component C9". Biochemistry. 27 (17): 6529–6534. doi:10.1021/bi00417a050. PMID 3219351.
^ Stanley KK; Luzio JP; Tschopp J; Kocher HP; Jackson P (1985). "The sequence and topology of human complement component C9". EMBO J. 4 (2): 375–382. doi:10.1002/j.1460-2075.1985.tb03639.x. PMC 554196. PMID 4018030.
^ Fey GH, Hugli TE, Podack ER, Gehring MR, Kan CC, DiScipio RG (1984). "Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9". Proc. Natl. Acad. Sci. U.S.A. 81 (23): 7298–7302. Bibcode:1984PNAS...81.7298D. doi:10.1073/pnas.81.23.7298. PMC 392133. PMID 6095282.

[pmid32194049-1] Xie CB, Jane-Wit D, Pober JS (2020). "Complement Membrane Attack Complex: New Roles, Mechanisms of Action, and Therapeutic Targets". The American Journal of Pathology. 190 (6): 1138–1150. doi:10.1016/j.ajpath.2020.02.006. PMC 7280757. PMID 32194049.

[Janeway_2001-2] Janeway, CA Jr; Travers P; Walport M; et al. (2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland Science. Retrieved 4 January 2018.

[PUB00000295-3] Stanley KK, Marazziti D, Eggertsen G, Fey GH (1988). "Relationships between the gene and protein structure in human complement component C9". Biochemistry. 27 (17): 6529–6534. doi:10.1021/bi00417a050. PMID 3219351.

[PUB00001141-4] Stanley KK; Luzio JP; Tschopp J; Kocher HP; Jackson P (1985). "The sequence and topology of human complement component C9". EMBO J. 4 (2): 375–382. doi:10.1002/j.1460-2075.1985.tb03639.x. PMC 554196. PMID 4018030.

[PUB00004608-5] Fey GH, Hugli TE, Podack ER, Gehring MR, Kan CC, DiScipio RG (1984). "Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9". Proc. Natl. Acad. Sci. U.S.A. 81 (23): 7298–7302. Bibcode:1984PNAS...81.7298D. doi:10.1073/pnas.81.23.7298. PMC 392133. PMID 6095282.

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