Article
- The EMBO Journal (2006) 25, 457 - 466
- doi:10.1038/sj.emboj.7600959
Published online: 19 January 2006
Subject Categories:
A rivet model for channel formation by aerolysin-like pore-forming toxins
Ioan Iacovache1,a, Patrick Paumard1,a, Holger Scheib2,3,4, Claire Lesieur1, Naomi Sakai5, Stefan Matile5, Michael W Parker6 and F Gisou van der Goot1
- Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
- Department of Structural Biology, University of Geneva, Geneva, Switzerland
- Swiss Institute of Bioinformatics, University of Geneva, Geneva, Switzerland
- SBC Lab AG, Winkel, Switzerland
- Department of Organic Chemistry, University of Geneva, Geneva, Switzerland
- Biota Structural Biology Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia
Correspondence to:
F Gisou van der Goot, Department of Genetics & Microbiology, CMU, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva 4, Switzerland. Tel.: +41 22 379 5652; Fax: +41 22 379 5896; E-mail: gisou.vandergoot@medecine.unige.ch
aThese authors contributed equally to this work
Received 23 June 2005; Accepted 16 December 2005
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 
-barrel configuration, as observed for Staphylococcal 
-toxin. Surprisingly, we found that the turn of the -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.
Keywords:
- -barrel,
- lipid bilayers,
- membrane proteins,
- pore-forming,
- toxin
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