The pore structure of Clostridium perfringens epsilon toxin

Christos G Savva (1) , Alice Clark (2) , Claire E Naylor (3) , Michel R. Popoff (4) , David Moss (5) , Ajit K Basak (5) , Richard Titball (6) , Monika Bokori-Brown (6)

1 LISCB - Leicester Institute of Structural and Chemical Biology [Leicester]
2 University of Wolverhampton
3 Molecular Dimensions Ltd [Newmarket]
4 Bactéries anaérobies et Toxines
5 Birkbeck College [University of London]
6 College of Life and Environmental Sciences [Exeter]

Epsilon toxin (Etx), a potent pore forming toxin (PFT) produced by Clostridium perfringens, is responsible for the pathogenesis of enterotoxaemia of ruminants and has been suggested to play a role in multiple sclerosis in humans. Etx is a member of the aerolysin family of β-PFTs (aβ-PFTs). While the Etx soluble monomer structure was solved in 2004, Etx pore structure has remained elusive due to the difficulty of isolating the pore complex. Here we show the cryo-electron microscopy structure of Etx pore assembled on the membrane of susceptible cells. The pore structure explains important mutant phenotypes and suggests that the double β-barrel, a common feature of the aβ-PFTs, may be an important structural element in driving efficient pore formation. These insights provide the framework for the development of novel therapeutics to prevent human and animal infections, and are relevant for nano-biotechnology applications.

Keywords: Cryoelectron microscopy; Bacterial toxins

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology; Life Sciences [q-bio]; Cellular Biology; Life Sciences [q-bio]; Cellular Biology; Subcellular Processes [q-bio.SC]; Life Sciences [q-bio]; Cellular Biology; Cell Behavior [q-bio.CB]

Christos G Savva, Alice Clark, Claire E Naylor, Michel R. Popoff, David Moss, et al.. The pore structure of Clostridium perfringens epsilon toxin. Nature Communications, 2019, 10 (1), pp.2641. ⟨10.1038/s41467-019-10645-8⟩. ⟨pasteur-02454060⟩