3c0n
Crystal structure of the proaerolysin mutant Y221G at 2.2 ACrystal structure of the proaerolysin mutant Y221G at 2.2 A
Structural highlights
FunctionAERA_AERHY Aerolysin is a cytolytic toxin exported by the Gram negative Aeromonas bacteria. The mature toxin binds to eukaryotic cells and aggregates to form holes approximately 3 nm in diameter, leading to destruction of the membrane permeability barrier and osmotic lysis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAerolysin is the founding member of a superfamily of beta-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 beta-barrel. Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism.,Degiacomi MT, Iacovache I, Pernot L, Chami M, Kudryashev M, Stahlberg H, van der Goot FG, Dal Peraro M Nat Chem Biol. 2013 Oct;9(10):623-9. doi: 10.1038/nchembio.1312. Epub 2013 Aug 4. PMID:23912165[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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