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

Degiacomi, M.T. and Iacovache, I. and Pernot, L. and Chami, M. and Kudryashev, M. and Stahlberg, H. and Van Der Goot, F.G. and Dal Peraro, M. (2013) 'Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism.', Nature chemical biology., 9 (10). pp. 623-629.

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.

Item Type:Article
Full text:(AM) Accepted Manuscript
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1038/nchembio.1312
Date accepted:25 June 2013
Date deposited:08 August 2017
Date of first online publication:04 August 2013
Date first made open access:No date available

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