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| Item Type: | Article |
|---|---|
| Title: | Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism |
| Creators Name: | Degiacomi, M.T., Iacovache, I., Pernot, L., Chami, M., Kudryashev, M., Stahlberg, H., 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 |
| ISSN: | 1552-4450 |
| Publisher: | Nature Publishing Group |
| Volume: | 9 |
| Number: | 10 |
| 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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