TY - JOUR
T1 - Insights into the Voltage Regulation Mechanism of the Pore-Forming Toxin Lysenin
AU - Bryant, Sheenah Lynn
AU - Clark, Tyler
AU - Thomas, Christopher Alex
AU - Ware, Kaitlyn Summer
AU - Bogard, Andrew
AU - Calzacorta, Colleen
AU - Prather, Daniel
AU - Fologea, Daniel
N1 - Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/8
Y1 - 2018/8
N2 - Lysenin, 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.
AB - Lysenin, 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.
KW - Electrostatic screening
KW - Hysteresis
KW - Lysenin
KW - Pore forming toxins
KW - Voltage gating
UR - http://www.scopus.com/inward/record.url?scp=85052529803&partnerID=8YFLogxK
UR - https://scholarworks.boisestate.edu/physics_facpubs/212
U2 - 10.3390/toxins10080334
DO - 10.3390/toxins10080334
M3 - Article
C2 - 30126104
VL - 10
JO - Toxins
JF - Toxins
IS - 8
M1 - 334
ER -