The MACPF/CDC family of pore-forming toxins.
Pore-forming toxins (PFTs) are commonly associated with bacterial pathogenesis. In eukaryotes, however, PFTs operate in the immune system or are deployed for attacking prey (e.g. venoms). This review focuses upon two families of globular protein PFTs: the cholesterol-dependent cytolysins (CDCs) and the membrane attack complex/perforin superfamily (MACPF). CDCs are produced by Gram-positive bacteria and lyse or permeabilize host cells or intracellular organelles during infection. In eukaryotes, MACPF proteins have both lytic and non-lytic roles and function in immunity, invasion and development. The structure and molecular mechanism of several CDCs are relatively well characterized. Pore formation involves oligomerization and assembly of soluble monomers into a ring-shaped pre-pore which undergoes conformational change to insert into membranes, forming a large amphipathic transmembrane beta-barrel. In contrast, the structure and mechanism of MACPF proteins has remained obscure. Recent crystallographic studies now reveal that although MACPF and CDCs are extremely divergent at the sequence level, they share a common fold. Together with biochemical studies, these structural data suggest that lytic MACPF proteins use a CDC-like mechanism of membrane disruption, and will help understand the roles these proteins play in immunity and development.
Department of Biochemistry, Monash University, Clayton, Victoria 3800, Australia.
Carlos J
CJ
Rosado
Stephanie
S
Kondos
Tara E
TE
Bull
Michael J
MJ
Kuiper
Ruby H P
RH
Law
Ashley M
AM
Buckle
Ilia
I
Voskoboinik
Phillip I
PI
Bird
Joseph A
JA
Trapani
James C
JC
Whisstock
Michelle A
MA
Dunstone
D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000276:immunology*; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000737:chemistry* / Q000276:immunology*; D018360:Crystallography, X-Ray; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D015388:Organelles / Q000737:chemistry / Q000276:immunology; D054353:Perforin / Q000737:chemistry* / Q000276:immunology*; D017433:Protein Structure, Secondary
D001427:Bacterial Toxins; D015938:Complement Membrane Attack Complex; D054353:Perforin