Cryo-EM structure of the octameric pore of Clostridium perfringens β-toxin
Clostridium perfringens is one of the most widely distributed and successful pathogens. It causes multiple severe diseases in animals and humans and produces an impressive arsenal of toxins with pore-forming properties, most of them belonging to the hemolysin-like family of {beta}-pore forming toxins ({beta}-PFTs). One of the most potent toxins produced by C. perfringens is {beta}-toxin (CPB). This toxin is the main virulence factor of type C strains and essential for the development of a fatal necrotic enteritis in humans and newborn animals. In the present study, we describe the cryo-electron microscopy (cryo-EM) structure of CPB in styrene maleic acid (SMA) discs, which represents the membrane-inserted pore form, at near atomic resolution. We show that CPB forms a homo-oligomeric pore with eightfold symmetry and similar conformation to the hetero-oligomeric pores of the bi-component leukocidins, with important differences in the receptor binding region and the N-terminal latch domain. Intriguingly, the octameric CPB pore complex contains a second 16-stranded {beta}-barrel protrusion atop of the cap domain that is formed by the N-termini of the eight protomers. We propose that CPB defines a new subclass of the hemolysin-like family of {beta}-PFTs s. In addition, we show that the {beta}-barrel protrusion domain can be changed or modified without affecting the pore forming ability, thus making the pore particularly attractive for macromolecule sensing and nanotechnology. The cryo-EM structure of the octameric pore of CPB will facilitate future developments in both nanotechnology and basic research.