MACPF
| MAC/Perforin domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | MACPF | ||||||||
| Pfam | PF01823 | ||||||||
| InterPro | IPR001862 | ||||||||
| SMART | MACPF | ||||||||
| PROSITE | PDOC00251 | ||||||||
| TCDB | 1.C.39 | ||||||||
|
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| Available protein structures: | |
|---|---|
| Pfam | structures |
| PDB | RCSB PDB; PDBe; PDBj |
| PDBsum | structure summary |
The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily, 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). In eukaryotes, MACPF proteins play a role in immunity and development.
Archetypal members of the family are complement C9 and perforin, both of which function in human immunity. 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. Deficiency of either protein can result in human disease. 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.
As of early 2016, there are three families belonging to the MACPF superfamily:
Proteins containing MACPF domains play key roles in vertebrate immunity, embryonic development, and neural-cell migration. The ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. The crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens was determined (PDB: 2QP2). The MACPF domain is structurally similar to pore-forming cholesterol-dependent cytolysins from gram-positive bacteria, suggesting that MACPF proteins create pores and disrupt cell membranes similar to cytolysin. A representative list of proteins belonging to the MACPF family can be found in the Transporter Classification Database.
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