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Nat Chem Biol. 2013 Oct;9(10):623-9. doi: 10.1038/nchembio.1312. Epub 2013 Aug 4.

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

Author information

1
1] Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. [2] [3].

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.

PMID:
23912165
DOI:
10.1038/nchembio.1312
[Indexed for MEDLINE]

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