Pore-forming toxins: ancient, but never really out of fashion

Pore-forming toxins (PFTs), which are expressed as virulence factors by many pathogenic bacteria, and pore-forming proteins (PFPs) have been found in all kingdoms of lifePFTs and PFPs undergo a structural and functional metamorphosis from soluble, inactive monomers to active, complex multimeric transmembrane pores that insert into the membranes of target cellsBased on their structure and mechanism of pore formation, six families of PFTs and PFPs have been described, each of which has a distinct structure and mechanism of pore formation. These families can be grouped into two larger classes, α-PFTs and β-PFTs (or PFPs), based on the secondary structures of their transmembrane pore domainsOwing to substantial recent advances in the structural biology of PFTs, we are beginning to understand the pore architecture and the mechanism of pore formation for all six familiesThe specificity of PFTs and PFPs is determined by their interactions with lipids, sugars and/or protein receptors present in, or on, the target cell membraneStructural modularity enables toxins with the same pore-forming mechanism to target different host cell types by binding to different receptorsFor PFTs that contribute to infection, examining their structures, dynamics and interactions with host cells at molecular resolution provides cues for the development of therapeutics that could be highly effective in fighting disease