Bacterial membrane toxin assemblies, such as α-hemolysin from Staph. A., anthrax lethal toxin, and cytolysin A from E. coli, are major virulence factors for these disease-causing organisms. Native ion mobility-mass spectrometry (IM-MS) has previously demonstrated that anthrax lethal toxin adopts two soluble pre-pore oligomeric states, heptamer and octamer, the latter of which is more stable in acidic environments and increases the virulence of the toxin during infection. Structural studies of α-hemolysin and cytolysin A indicate they may also have multiple native oligomeric states, but studying the pore form of these toxins is complicated by the need for a detergent or lipid environment for stability. Here, we show how Gábor Transform-based native IM-MS methods, in combination with molecular dynamics simulations, can be used to identify the olgomeric state distribution of the pore forms of these toxins embedded in intact detergent and lipid nano-environments as well as characterize the shape and size of their native structures. Finally, we use native IM-MS to characterize the preference of these toxin proteins for raft-associated lipids.

Investigation of membrane toxin assemblies with native ion mobility-mass spectrometry and Gábor transform

2019 Fall National Meeting

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