Poster Presentation The 45th Lorne Conference on Protein Structure and Function 2020

Structural insights into Type II ABC Tc cell recognition (#324)

Joseph K Box 1 , Sarah J Piper 1 , Lou Brillault 1 , Tristan Croll 2 , Jason Busby 3 , Shaun J Lott 3 , Andrew Leis 4 , Eric Hanssen 4
  1. University of Queensland, Saint Lucia, QLD, Australia
  2. Institute for Medical Research, Cambridge University, Cambridge, United Kingdom
  3. School of Biological Sciences, University of Auckland, Auckland, New Zealand
  4. Bio21, University of Melbourne, Melbourne, Australia

ABC toxin complexes (Tc) are large macro-molecular pore forming toxins, named because they are a product of a minimum of three genes; TcA, TcB, and TcC in a 5:1:1 stoichiometry. They are major determinants of toxicity in insect and vertebrate (including human) pathogens and have been linked to virulence. As such, there is potential to exploit ABC Tcs in the development of novel bio-pesticides and the design of antimicrobials that attenuate virulence. Employing hybrid CryoEM, crystallographic, and atomic modeling techniques, we have recently determined the first structure of a Type 2 ABC Tc, YenTc found in the entomopathogenic Yersinia entomophaga to near atomic resolution in its pre-pore forming state. Work presented here is focused on the A subunit of YenTc and has allowed us to suggest an interesting mode of cell recognition that differs from that of Type 1 Tcs. Lead by structural and functional data, we endeavour to re-engineer YenTcA into a novel toxin delivery system.