title: A rivet model for channel formation by aerolysin-like pore-forming toxins.
abstract: 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 beta-barrel configuration, as observed for Staphylococcal alpha-toxin. Surprisingly, we found that the turn of the beta-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.
authors.affiliation: Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Ioan
authors.initials: I
authors.lastname: Iacovache
authors.forename: Patrick
authors.initials: P
authors.lastname: Paumard
authors.forename: Holger
authors.initials: H
authors.lastname: Scheib
authors.forename: Claire
authors.initials: C
authors.lastname: Lesieur
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakai
authors.forename: Stefan
authors.initials: S
authors.lastname: Matile
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
authors.forename: F Gisou
authors.initials: FG
authors.lastname: van der Goot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D006224:Cricetinae; D003545:Cysteine / Q000737:chemistry; D007473:Ion Channels / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D052899:Pore Forming Cytotoxic Proteins; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001427:Bacterial Toxins; D007473:Ion Channels; D008051:Lipid Bilayers; D052899:Pore Forming Cytotoxic Proteins; C032676:aerolysin; D003545:Cysteine