Anthrax edema factor, voltage-dependent binding to the protective antigen ion channel and comparison to LF binding

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Abstract

Anthrax toxin complex consists of three different molecules, the binding component protective antigen (PA, 83 kDa), and the enzymatic components lethal factor (LF, 90 kDa) and edema factor (EF, 89 kDa). The 63-kDa N-terminal part of PA, PA63, forms a heptameric channel that inserts at low pH in endosomal membranes and that is necessary to translocate EF and LF in the cytosol of the target cells. EF is an intracellular active enzyme, which is a calmodulin-dependent adenylate cyclase (89 kDa) that causes a dramatic increase of intracellular cAMP level. Here, the binding of full-length EF on heptameric PA63 channels was studied in experiments with artificial lipid bilayer membranes. Full-length EF blocks the PA63 channels in a dose, temperature, voltage, and ionic strength-dependent way with half-saturation constants in the nanomolar concentration range. EF only blocked the PA 63 channels when PA63 and EF were added to the same side of the membrane, the cis side. Decreasing ionic strength and increasing transmembrane voltage at the cis side of the membranes resulted in a strong decrease of the half-saturation constant for EF binding. This result suggests that ion-ion interactions are involved in EF binding to the PA heptamer. Increasing temperature resulted in increasing half-saturation constants for EF binding to the PA63 channels. The binding characteristics of EF to the PA63 channels are compared with those of LF binding. The comparison exhibits similarities but also remarkable differences between the bindings of both toxins to the PA63 channel. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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Neumeyer, T., Tonello, F., Dal Molin, F., Schiffler, B., & Benz, R. (2006). Anthrax edema factor, voltage-dependent binding to the protective antigen ion channel and comparison to LF binding. Journal of Biological Chemistry, 281(43), 32335–32343. https://doi.org/10.1074/jbc.M606552200

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