The ABC toxins are large (>1.7 MDa) pore-forming protein complexes and the main virulence factors of a variety of pathogenic, Gram-negative bacteria. Due to their insecticidal activity, they have potential implications as novel biopesticides. Additionally, their possible involvement in human disease, together with their modular architecture and mechanism of action, suggest they also have the potential for the development of targeted drug delivery systems. Protein complexes from the ABC toxin family are currently thought to recognise their hosts through high-specificity interactions between their receptor-binding domains and cell-surface glycans/glycosylated receptors on the plasma membrane.
We are currently studying the structure and molecular mechanisms of YenTc- an ABC toxin secreted by the insect pathogen Yersinia entomophaga. Despite having previously solved the structure of YenTc using cryo-EM, the mechanisms of how it recognises its target cells remain poorly understood. To address this, we have focused on the structure and function of the Chi1 and Chi2 putative receptor-binding domains of YenTc, specifically how they recognise and bind to cell-surface glycans. In solving the crystal structure of Chi1, we uncovered functionally important cis-peptides in the catalytic cleft of the enzyme that was not reported previously. In addition, we have utilized live cell imaging to investigate how cell surface glycans influence the dynamics of YenTc cell internalisation. Finally, we have determined the structure of another member of the ABC toxin family, SepABC, with an overlapping but distinct host specificity profile to YenTs in an effort to understand whether its structural features explain the observed difference in host specificity.