page_title: MACPF
section_title: Control of MACPF proteins
hierarchical_section_title: MACPF / Control of MACPF proteins
caption_attribution_description: English: Structure of the MAC inhibitor CD59 - PDB 1ERG picture made using pymol.
context_page_description: The Membrane Attack Complex/Perforin superfamily, sometimes referred to as the MACPF/CDC superfamily, is named after a domain that is common to the membrane attack complex proteins of the complement system and perforin. Members of this protein family are pore-forming toxins. 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, a family of pore forming toxins previously thought to only exist in bacteria.
context_section_description: Complement regulatory proteins such as CD59 function as MAC inhibitors and prevent inappropriate activity of complement against self cells (Figure 3).  Biochemical studies have revealed the peptide sequences in C8α and C9 that bind to CD59.  Analysis of the MACPF domain structures reveals that these sequences map to the second cluster of helices that unfurl to span the membrane. It is therefore suggested that CD59 directly inhibits the MAC by interfering with conformational change in one of the membrane spanning regions.
  Other proteins that bind to the MAC include C8γ. This protein belongs to the lipocalin family and interacts with C8α. The binding site on C8α is known, however, the precise role of C8γ in the MAC remains to be understood.
caption: Figure 3: NMR structure of CD59.[28] [3].
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