Oral Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Structural insights into the mechanism of host cell recognition by a type II bacterial toxin complex (#34)

Sarah J Piper 1 , Tristan Croll 2 , Lou Brillault 1 , Rosalba Rothnagel 1 , Sebastian Scherer 3 , Jason N Busby 4 , Shaun Lott 4 , Henning Stahlberg 3 , Mark RH Hurst 5 , Michael J Landsberg 6
  1. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
  2. Institute for Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia
  3. Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Basel, Switzerland
  4. School of Biological Sciences, University of Auckland, Auckland, New Zealand
  5. Innovative Farm Systems, AgResearch Ltd., Lincoln, New Zealand
  6. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia

ABC toxins are large (1.5-2.5 MDa), tripartite pore-forming 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 characteristically trigger apoptotic cell death by delivering cytotoxins that target the actin polymerization pathway to selectively targeted host cells.  Genes encoding related toxins are also found in bacterial pathogens of significance to humans although their role in virulence remains unclear.  Recent advances in single particle cryo-electron microscopy have allowed the mechanism by which prototypical bacterial ABC toxin systems package, translocate and deliver potent cytotoxins to targeted inter-cellular destinations to be visualised in near-atomic detail.  Here we will focus on insights obtained from the first near-atomic resolution structure of a representative type II toxin – the 2.3 MDa YenTc from the insect pathogen Yersinia entomophaga.  Our results suggest YenTc has a distinctive mechanism of cell surface recognition and provide the first clues as to the identity of candidate ligands that direct their interaction with epithelial cell surfaces.  We show that YenTc is capable of forming a transmembrane pore, but in contrast with previously characterized type I toxins from Photorhabdus luminescens, formation of the pore is only weakly stimulated by extreme pH. Our results therefore challenge the prevailing paradigm of how pore-formation is triggered physiologically.