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From Proteopedia
Aerolysin E254A/E258A in styrene-maleic acid lipid particles
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. Publication Abstract from PubMedbeta-Barrel nanopores are involved in crucial biological processes, from ATP export in mitochondria to bacterial resistance, and represent a promising platform for emerging sequencing technologies. However, in contrast to ion channels, the understanding of the fundamental principles governing ion transport through these nanopores remains largely unexplored. Here we integrate experimental, numerical and theoretical approaches to elucidate ion transport mechanisms in beta-barrel nanopores. We identify and characterize two distinct nonlinear phenomena: open-pore rectification and gating. Through extensive mutation analysis of aerolysin nanopores, we demonstrate that open-pore rectification is caused by ionic accumulation driven by the distribution of lumen charges. In addition, we provide converging evidence suggesting that gating is controlled by electric fields dissociating counterions from lumen charges, promoting local structural deformations. Our findings establish a rigorous framework for characterizing and understanding ion transport processes in protein-based nanopores, enabling the design of adaptable nanofluidic biotechnologies. We illustrate this by optimizing an aerolysin mutant for computing applications. Lumen charge governs gated ion transport in beta-barrel nanopores.,Mayer SF, Mitsioni MF, Robin P, van den Heuvel L, Ronceray N, Marcaida MJ, Abriata LA, Krapp LF, Anton JS, Soussou S, Jeanneret-Grosjean J, Fulciniti A, Moller A, Vacle S, Feletti L, Brinkerhoff H, Laszlo AH, Gundlach JH, Emmerich T, Dal Peraro M, Radenovic A Nat Nanotechnol. 2025 Nov 11. doi: 10.1038/s41565-025-02052-6. PMID:41219410[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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