Key result
High electric fields close bacterial OmpF channels via reversible protein denaturation rather than functional gating.
Why the study?
To explore the hypothesis that voltage-induced closure of beta-barrel channels represents reversible protein denaturation by high electric fields rather than functional gating.
Voltage-induced closure of beta-barrel channels in high electric fields may represent reversible protein denaturation rather than functional gating, potentially serving as an evolutionary precursor to voltage-gated channels.
Challenges prior gating interpretations in beta-barrel studies; leaves open evolutionary origins of voltage sensing in ion channels.
Ion channels exhibit gating behavior, fluctuating between open and closed states, with the transmembrane voltage serving as one of the essential regulators of this process. Voltage gating is a fundamental functional aspect underlying the regulation of ion-selective, mostly α-helical, channels primarily found in excitable cell membranes. In contrast, there exists another group of larger, and less selective, β-barrel channels of a different origin, which are not directly associated with cell excitability. Remarkably, these channels can also undergo closing, or "gating", induced by sufficiently strong electric fields. Once the field is removed, the channels reopen, preserving a memory of the gating process. In this study, we explored the hypothesis that the voltage-induced closure of the β-barrel channels can be seen as a form of reversible protein denaturation by the high electric fields applied in model membranes experiments-typically exceeding twenty million volts per meter-rather than a manifestation of functional gating. Here, we focused on the bacterial outer membrane channel OmpF reconstituted into planar lipid bilayers and analyzed various characteristics of the closing-opening process that support this idea. Specifically, we considered the nearly symmetric response to voltages of both polarities, the presence of multiple closed states, the stabilization of the open conformation in channel clusters, the long-term gating memory, and the Hofmeister effects in closing kinetics. Furthermore, we contemplate the evolutionary aspect of the phenomenon, proposing that the field-induced denaturation of membrane proteins might have served as a starting point for their development into amazing molecular machines such as voltage-gated channels of nerve and muscle cells.
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Nestorovich et al. (2023) studied Bacterial outer membrane channel OmpF in planar lipid bilayers. High electric fields was evaluated on Characteristics of the closing-opening process. High electric fields induced closure of bacterial OmpF channels in planar lipid bilayers, exhibiting characteristics consistent with reversible protein denaturation rather than functional gating.
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