A rivet model for channel formation by aerolysin‐like pore‐forming toxins
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 alterna...
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Published in | The EMBO journal Vol. 25; no. 3; pp. 457 - 466 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
08.02.2006
Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work |
ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1038/sj.emboj.7600959 |