- Iacovache, I.; Paumard, P.; Scheib, H.; Lesieur, C.; Sakai, N.; Matile, S.; Parker, M. W.; van der Goot, F. G. “A Rivet Model for Channel Formation by Aerolysin-like Pore-Forming Toxins” EMBO J. 2006, 25, 457-466
The bacterial toxin aerolysin kills cells by forming heptameric channels, of unknown structure, in the plasma membrane. Using disulfide trapping and cysteine scanning mutagenesis coupled to thiol‐specific labeling on lipid bilayers, we identify a loop that lines the channel. This loop has an alternating pattern of charged and uncharged residues, suggesting that the transmembrane region has a β‐barrel configuration, as observed for Staphylococcal α‐toxin. Surprisingly, we found that the turn of the β‐hairpin is composed of a stretch of five hydrophobic residues. We show that this hydrophobic turn drives membrane insertion of the developing channel and propose that, once the lipid bilayer has been crossed, it folds back parallel to the plane of the membrane in a rivet‐like fashion. This rivet‐like conformation was modeled and sequence alignments suggest that such channel riveting may operate for many other pore‐forming toxins.