Matteo Degiacomi matteo.t.degiacomi@durham.ac.uk
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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.
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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