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

Details

Serval ID
serval:BIB_BEA9868C39AD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism.
Journal
Nature chemical biology
Author(s)
Degiacomi M.T., Iacovache I., Pernot L., Chami M., Kudryashev M., Stahlberg H., van der Goot F.G., Dal Peraro M.
ISSN
1552-4469 (Electronic)
ISSN-L
1552-4450
Publication state
Published
Issued date
10/2013
Peer-reviewed
Oui
Volume
9
Number
10
Pages
623-629
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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/chemistry, Bacterial Toxins/chemistry, Bacterial Toxins/genetics, Bacterial Toxins/metabolism, Crystallography, X-Ray, Membrane Proteins/chemistry, Membrane Proteins/genetics, Membrane Proteins/metabolism, Models, Molecular, Molecular Dynamics Simulation, Point Mutation, Pore Forming Cytotoxic Proteins/chemistry, Pore Forming Cytotoxic Proteins/genetics, Pore Forming Cytotoxic Proteins/metabolism, Protein Conformation
Pubmed
Web of science
Create date
09/06/2023 15:03
Last modification date
20/07/2023 5:57
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