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

Item Type:Article
Title:Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism
Creators Name: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.
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.
Keywords:Aeromonas salmonicida, Bacterial Toxins, Membrane Proteins, Molecular Dynamics Simulation, Molecular Models, Point Mutation, Pore Forming Cytotoxic Proteins, Protein Conformation, X-Ray Crystallography
Source:Nature Chemical Biology
Publisher:Nature Publishing Group
Page Range:623-629
Date:October 2013
Official Publication:https://doi.org/10.1038/nchembio.1312
PubMed:View item in PubMed

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