The membrane attack complex/perforin (MACPF) domain is conserved in bacteria, fungi, mammals and plants. It was originally identified and named as being common to five complement components (C6, C7, C8-alpha, C8-beta, and C9) and perforin. These molecules perform critical functions in innate and adaptive immunity. The MAC family proteins and perforin are known to participate in lytic pore formation. … expand

The membrane attack complex/perforin (MACPF) domain is conserved in bacteria, fungi, mammals and plants. It was originally identified and named as being common to five complement components (C6, C7, C8-alpha, C8-beta, and C9) and perforin. These molecules perform critical functions in innate and adaptive immunity. The MAC family proteins and perforin are known to participate in lytic pore formation. In response to pathogen infection, a sequential and highly specific interaction between the constituent elements occurs to form transmembrane channels which are known as the membrane-attack complex (MAC).Only a few other MACPF proteins have been characterised and several are thought to form pores for invasion or protection [ PUBMED:16900325 PUBMED:17717151 PUBMED:18440555 ]. Examples are proteins from malarial parasites [ PUBMED:15659064 ], the cytolytic toxins from sea anemones [ PUBMED:17368498 ], and proteins that provide plant immunity [ PUBMED:16900325 PUBMED:15799997 ]. Functionally uncharacterised MACPF proteins are also evident in pathogenic bacteria such as Chlamydia spp [ PUBMED:10608922 ] and Photorhabdus luminescens (Xenorhabdus luminescens) [ PUBMED:17717151 ].

The MACPF domain is commonly found to be associated with other N- and C-terminal domains, such as TSP1 LDLRA EGF-like,Sushi/CCP/SCR FIMAC or C2. They probably control or target MACPF function [ PUBMED:17717151 PUBMED:17872444 ]. The MACPF domain oligomerizes, undergoes conformational change, and is required for lytic activity.

The MACPF domain consists of a central kinked four-stranded antiparallel β sheet surrounded by α helices and β strands, forming two structural segments. Overall, the MACPF domain has a thin L-shaped appearance. MACPF domains exhibit limited sequence similarity but contain a signature [YW]-G-[TS]-H-[FY]-x(6)-G-G motif [ PUBMED:17717151 PUBMED:18440555 PUBMED:17872444 ].

Some proteins known to contain a MACPF domain are listed below:

• Vertebrate complement proteins C6 to C9. Complement factors C6 to C9 assemble to form a scaffold, the membrane attack complex (MAC), that permits C9 polymerisation into pores that lyse Gram-negative pathogens [ PUBMED:18440555 PUBMED:17872444 ].
• Vertebrate perforin. It is delivered by natural killer cells and cytotoxic T lymphocytes and forms oligomeric pores (12 to 18 monomers) in the plasma membrane of either virus-infected or transformed cells.
• Arabidopsis thaliana (Mouse-ear cress) constitutively activated cell death 1 (CAD1) protein. It is likely to act as a mediator that recognises plant signals for pathogen infection [ PUBMED:15799997 ].
• Arabidopsis thaliana (Mouse-ear cress) necrotic spotted lesions 1 (NSL1) protein [ PUBMED:16900325 ].
• Venomous sea anemone Phyllodiscus semoni (Night anemone) toxins PsTX-60A and PsTX-60B [ PUBMED:17368498 ].
• Venomous sea anemone Actineria villosa (Okinawan sea anemone) toxin AvTX-60A [ PUBMED:17368498 ].
• Plasmodium sporozoite microneme protein essential for cell traversal 2 (SPECT2). It is essential for the membrane-wounding activity of the sporozoite and is involved in its traversal of the sinusoidal cell layer prior to hepatocyte-infection [ PUBMED:15659064 ].
• P. luminescens Plu-MACPF. Although nonlytic, it was shown to bind to cell membranes [ PUBMED:17717151 ].
• Chlamydial putative uncharacterised protein CT153 [ PUBMED:10608922 ].