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

Degiacomi, M.T.; Iacovache, I.; Pernot, L.; Chami, M.; Kudryashev, M.; Stahlberg, H.; Van Der Goot, F.G.; Dal Peraro, M.

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Authors

I. Iacovache

L. Pernot

M. Chami

M. Kudryashev

H. Stahlberg

F.G. Van Der Goot

M. Dal Peraro



Abstract

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.

Citation

Degiacomi, M., Iacovache, I., Pernot, L., Chami, M., Kudryashev, M., Stahlberg, H., …Dal Peraro, M. (2013). Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism. Nature Chemical Biology, 9(10), 623-629. https://doi.org/10.1038/nchembio.1312

Journal Article Type Article
Acceptance Date Jun 25, 2013
Online Publication Date Aug 4, 2013
Publication Date Aug 4, 2013
Deposit Date Jul 26, 2017
Publicly Available Date Aug 8, 2017
Journal Nature Chemical Biology
Print ISSN 1552-4450
Electronic ISSN 1552-4469
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 9
Issue 10
Pages 623-629
DOI https://doi.org/10.1038/nchembio.1312
Public URL https://durham-repository.worktribe.com/output/1380826

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