Membrane curvature during membrane rupture and formation of pentagonal pyramidal superassemblies by a pore-forming toxin, Vibrio cholerae Cytolysin, using single particle cryo-EM

In this cryo-electron microscopy study, we provide mechanistic insights into how an archetypical {beta}-barrel pore-forming toxin ({beta}-PFT), Vibrio cholerae Cytolysin (VCC), ruptures the membrane lipid bilayer by inducing membrane curvature. We demonstrate how VCC oligomers cluster together and drastically increase local membrane curvature, thereby causing membrane blebbing. In addition, we also show how these PFTs after rupturing the host membrane tend to form symmetric super-molecular assemblies to stabilize their hydrophobic transmembrane rim domains. We further provide another example of membrane rupture with gamma hemolysin, a Staphylococcal bicomponent {beta}-PFT. These insights will usher new studies on membrane curvature due to protein crowding and broaden our mechanistic understanding of how this largest class of bacterial protein toxins induce host cellular death.