[Research progress on the MACPF/CDC family of pore-forming toxins]

Pore-forming toxins (PFTs) are commonly associated with bacterial and other prokaryote pathogenesis. In eukaryotes, PFTs play important roles in immunity, embryonic development and neural-cell migration. Two families of globular protein PFTs: the cholesterol-dependent cytolysins (CDCs) and the membrane attack complex/perforin superfamily (MACPF), arrest researchers' attention due to their unique molecular configuration and the function. CDCs are produced by Gram-positive bacteria and disrupt the membrane of host cells during infection. In eukaryotes, MACPF proteins have both lytic and non-lytic roles. With perfringolysin O (PFO) for example, the structure and molecular mechanism of CDCs are relatively well characterized. Recently crystallographic together with biochemical studies revealed that although MACPF and CDCs were extremely divergent at the amino acid sequence level, their common fold suggests that lytic MACPF proteins use a CDC-like mechanism of membrane disruption. This paper focuses on the structure, molecular mechanism of pore-formation and the research hotspot of the two families of PFTs, providing valuable clues for the future research in this field.