Insights into the Voltage Regulation Mechanism of the Pore-Forming Toxin Lysenin
AbstractLysenin, a pore forming toxin (PFT) extracted from Eisenia fetida, inserts voltage-regulated channels into artificial lipid membranes containing sphingomyelin. The voltage-induced gating leads to a strong static hysteresis in conductance, which endows lysenin with molecular memory capabilities. To explain this history-dependent behavior, we hypothesized a gating mechanism that implies the movement of a voltage domain sensor from an aqueous environment into the hydrophobic core of the membrane under the influence of an external electric field. In this work, we employed electrophysiology approaches to investigate the effects of ionic screening elicited by metal cations on the voltage-induced gating and hysteresis in conductance of lysenin channels exposed to oscillatory voltage stimuli. Our experimental data show that screening of the voltage sensor domain strongly affects the voltage regulation only during inactivation (channel closing). In contrast, channel reactivation (reopening) presents a more stable, almost invariant voltage dependency. Additionally, in the presence of anionic Adenosine 5′-triphosphate (ATP), which binds at a different site in the channel’s structure and occludes the conducting pathway, both inactivation and reactivation pathways are significantly affected. Therefore, the movement of the voltage domain sensor into a physically different environment that precludes electrostatically bound ions may be an integral part of the gating mechanism. View Full-Text
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Bryant, S.L.; Clark, T.; Thomas, C.A.; Ware, K.S.; Bogard, A.; Calzacorta, C.; Prather, D.; Fologea, D. Insights into the Voltage Regulation Mechanism of the Pore-Forming Toxin Lysenin. Toxins 2018, 10, 334.
Bryant SL, Clark T, Thomas CA, Ware KS, Bogard A, Calzacorta C, Prather D, Fologea D. Insights into the Voltage Regulation Mechanism of the Pore-Forming Toxin Lysenin. Toxins. 2018; 10(8):334.Chicago/Turabian Style
Bryant, Sheenah L.; Clark, Tyler; Thomas, Christopher A.; Ware, Kaitlyn S.; Bogard, Andrew; Calzacorta, Colleen; Prather, Daniel; Fologea, Daniel. 2018. "Insights into the Voltage Regulation Mechanism of the Pore-Forming Toxin Lysenin." Toxins 10, no. 8: 334.
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