MACPF

See also: Complement membrane attack complex
MAC/Perforin domain
Identifiers
SymbolMACPF
PfamPF01823
Pfam clanCDC
InterProIPR001862
SMARTMACPF
PROSITEPDOC00251
TCDB1.C.39
OPM superfamily168
OPM protein6h04
Membranome233
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily,[1] is named after a domain that is common to the membrane attack complex (MAC) proteins of the complement system (C6, C7, C8α, C8β and C9) and perforin (PF). Members of this protein family are pore-forming toxins (PFTs).[2] In eukaryotes, MACPF proteins play a role in immunity and development.[3]

Archetypal members of the family are complement C9 and perforin, both of which function in human immunity.[4] C9 functions by punching holes in the membranes of Gram-negative bacteria. Perforin is released by cytotoxic T cells and lyses virally infected and transformed cells. In addition, perforin permits delivery of cytotoxic proteases called granzymes that cause cell death.[5] Deficiency of either protein can result in human disease.[6][7] Structural studies reveal that MACPF domains are related to cholesterol-dependent cytolysins (CDCs), a family of pore forming toxins previously thought to only exist in bacteria.[8][9]

  1. ^ Gilbert, Robert J. C.; Mikelj, Miha; Dalla Serra, Mauro; Froelich, Christopher J.; Anderluh, Gregor (1 June 2013). "Effects of MACPF/CDC proteins on lipid membranes". Cellular and Molecular Life Sciences. 70 (12): 2083–2098. doi:10.1007/s00018-012-1153-8. ISSN 1420-9071. PMC 11114033. PMID 22983385. S2CID 17084919.
  2. ^ Peitsch MC, Tschopp J (1991). "Assembly of macromolecular pores by immune defense systems". Curr. Opin. Cell Biol. 3 (4): 710–6. doi:10.1016/0955-0674(91)90045-Z. PMID 1722985.
  3. ^ Rosado, Carlos J.; Kondos, Stephanie; Bull, Tara E.; Kuiper, Michael J.; Law, Ruby H. P.; Buckle, Ashley M.; Voskoboinik, Ilia; Bird, Phillip I.; Trapani, Joseph A. (1 September 2008). "The MACPF/CDC family of pore-forming toxins". Cellular Microbiology. 10 (9): 1765–1774. doi:10.1111/j.1462-5822.2008.01191.x. ISSN 1462-5822. PMC 2654483. PMID 18564372.
  4. ^ Tschopp J, Masson D, Stanley KK (1986). "Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis". Nature. 322 (6082): 831–4. Bibcode:1986Natur.322..831T. doi:10.1038/322831a0. PMID 2427956. S2CID 4330219.
  5. ^ Voskoboinik I, Smyth MJ, Trapani JA (2006). "Perforin-mediated target-cell death and immune homeostasis". Nat. Rev. Immunol. 6 (12): 940–52. doi:10.1038/nri1983. PMID 17124515. S2CID 39504110.
  6. ^ Voskoboinik I, Sutton VR, Ciccone A, et al. (2007). "Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function". Blood. 110 (4): 1184–90. doi:10.1182/blood-2007-02-072850. PMID 17475905.
  7. ^ Witzel-Schlömp K, Späth PJ, Hobart MJ, et al. (1997). "The human complement C9 gene: identification of two mutations causing deficiency and revision of the gene structure". J. Immunol. 158 (10): 5043–9. doi:10.4049/jimmunol.158.10.5043. PMID 9144525. S2CID 22684521.
  8. ^ Rosado CJ, Buckle AM, Law RH, et al. (2007). "A Common Fold Mediates Vertebrate Defense and Bacterial Attack". Science. 317 (5844): 1548–51. Bibcode:2007Sci...317.1548R. doi:10.1126/science.1144706. PMID 17717151. S2CID 20372720.
  9. ^ Michael A. Hadders; Dennis X. Beringer & Piet Gros (2007). "Structure of C8-MACPF Reveals Mechanism of Membrane Attack in Complement Immune Defense". Science. 317 (5844): 1552–1554. doi:10.1126/science.1147103. hdl:1874/26831. PMID 17872444. S2CID 44959101.