The MACPF/CDC family of pore-forming toxins

Carlos Joaquim Rosado, Stephanie Kondos, Tara Elaina Bull, Michael Kuiper, Ruby Hong Ping Law, Ashley Maurice Buckle, Ilia Voskoboinik, Phillip Ian Bird, Joseph A Trapani, James Whisstock, Michelle Anne Dunstone

Research output: Contribution to journalArticleResearchpeer-review

187 Citations (Scopus)

Abstract

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 characterised. Pore formation involves oligomerisation 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.
Original languageEnglish
Pages (from-to)1765 - 1774
Number of pages10
JournalCellular Microbiology
Volume10
Issue number9
Publication statusPublished - 2008

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