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Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Degiacomi Matteo T, Iacovache Ioan, Pernot Lucile, Chami Mohamed, Kudryashev Misha, Stahlberg Henning, van der Goot F Gisou, Dal Peraro Matteo,
Project Software for Electron Microscopy of Membrane Proteins
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Original article (peer-reviewed)

Journal Nature chemical biology
Volume (Issue) 9(10)
Page(s) 623 - 9
Title of proceedings Nature chemical biology
DOI 10.1038/nchembio.1312


Aerolysin is the founding member of a superfamily of β-pore-forming toxins whose pore structure is unknown. We have combined X-ray crystallography, cryo-EM, molecular dynamics and computational modeling to determine the structures of aerolysin mutants in their monomeric and heptameric forms, trapped at various stages of the pore formation process. A dynamic modeling approach based on swarm intelligence was applied, whereby the intrinsic flexibility of aerolysin extracted from new X-ray structures was used to fully exploit the cryo-EM spatial restraints. Using this integrated strategy, we obtained a radically new arrangement of the prepore conformation and a near-atomistic structure of the aerolysin pore, which is fully consistent with all of the biochemical data available so far. Upon transition from the prepore to pore, the aerolysin heptamer shows a unique concerted swirling movement, accompanied by a vertical collapse of the complex, ultimately leading to the insertion of a transmembrane β-barrel.