ABC toxins are large, tripartite protein toxins secreted by a wide range of Gram positive and Gram negative bacteria. They are the predominant virulence factors in many insecticidal bacteria, where they function as cytotoxins targeting the actin cytoskeleton of susceptible host cells, and trigger apoptotic cell death. Genes encoding related toxins have also been identified in bacterial pathogens of significance to humans, although their role in virulence is unclear. Moreover, it now appears that analogous mechanisms may be employed by eukaryotic cells for the generalised packaging and translocation of bioactive proteins, such as neuropeptides. 

Recent breakthroughs in the structural characterisation of bacterial ABC toxins have focused on two prototypical toxin systems - those secreted by the insecticidal bacteria Y. entomophaga and P. luminescens. These studies have revealed that the ABC toxin system represents a novel protein machinery that packages, translocates and targets bioactive proteins to targeted inter-cellular destinations. The work described here has combined single particle EM, X-ray crystallography and small angle X-ray scattering to investigate the structure of the prototypical Y. entomophaga ABC toxin.^1,2 The complex is comprised of 23 mature polypeptides assembled into three functionally distinct subunits - an oligomeric, pore forming subunit (subunit A), a chaperonin (subunit B) and a cytotoxic peptide (subunit C), encapsulated within the chaperonin and delivered via the transmembrane pore formed by the A subunit. Our EM studies demonstrated for the first time that the A is a pentameric assembly to which the BC sub-complex is peripherally attached, while our X-ray crystal structure of the BC sub-complex revealed the first insights into the mechanism of ABC toxins at atomic resolution. Finally, our most recent cryo-EM analyses suggest that the mechanism of cell membrane recognition by the Y. entomophaga toxin is different to that which has recently been proposed for the P. luminescens toxins.