The structure and function of mammalian membrane-attack complex/perforin-like proteins.
The membrane-attack complex (MAC) of complement pathway and perforin (PF) are important tools deployed by the immune system to target pathogens. Both perforin and the C9 component of the MAC contain a common 'MACPF' domain and form pores in the cell membrane as part of their function. The MAC targets gram-negative bacteria and certain pathogenic parasites, while perforin, released by natural killer cells or cytotoxic T lymphocytes (CTLs), targets virus-infected and transformed host cells (1). Remarkably, recent structural studies show that the MACPF domain is homologous to the pore-forming portion of bacterial cholesterol-dependent cytolysins; these data have provided important insight into the mechanism of pore-forming MACPF proteins. In addition to their role in immunity, MACPF family members have been identified as animal venoms, factors required for pathogen migration across host cell membranes and factors that govern developmental processes such as embryonic patterning and neuronal guidance (2). While most MACPF proteins characterized to date either form pores or span lipid membranes, some do not (e.g. the C6 component of the MAC). A current challenge is thus to understand the role, pore forming or otherwise, of MACPF proteins in developmental biology. This review discusses structural and functional diversity of the mammalian MACPF proteins.
Kondos
S C
SC
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Hatfaludi
T
T
Voskoboinik
I
I
Trapani
J A
JA
Law
R H P
RH
Whisstock
J C
JC
Dunstone
M A
MA
D000818:Animals; D018797:Cell Cycle Proteins; D015938:Complement Membrane Attack Complex / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054353:Perforin / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
C072976:Astn1 protein, mouse; C491992:BRINP1 protein, mouse; D018797:Cell Cycle Proteins; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D008565:Membrane Proteins; C483884:Mpeg1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C483885:Pfpl protein, mouse; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D020558:GTP Phosphohydrolases; C477972:GVINP1 protein, human; C477973:Gvin1 protein, mouse