Voltage sensor dynamics of a bacterial voltage-gated sodium channel NavAb reveal three conformational states

Han, Shuo; Vance, Joshua; Jones, S. D.; DeCata, Jenna; Tran, Kimberly; Wang, Shizhen

doi:10.1016/j.jbc.2023.102967

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…A two-layer Markov-Model depicting possible conformations for the sensor and the ring. The sensor in each subunit can independently adopt one of three conformations (up, middle, and down) (Han et al, 2023). The up conformation represents the active conformation.…”

Section: A Two-layer Markov Model Recapitulates the Kinetic Features ...mentioning

confidence: 99%

Revealing a hidden conducting state by manipulating the intracellular domains in K_V10.1 exposes the coupling between two gating mechanisms

Abdelaziz

Tomczak

Neef³

et al. 2023

Preprint

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TheKCNHfamily of potassium channels serves relevant physiological functions in both excitable and non-excitable cells, reflected in the massive consequences of mutations or pharmacological manipulation of their function. This group of channels shares structural homology with other voltage-gated K+channels. Still, the mechanisms of gating in this family show significant differences with respect to the canonical electromechanical coupling in these molecules. In particular, the large intracellular domains ofKCNHchannels play a crucial role in gating that is still only partly understood. UsingKCNH1(KV10.1) as a model, we have characterized the behavior of a series of modified channels that the current models could not explain. With electrophysiological and biochemical methods combined with mathematical modeling, we show that the behavior of the mutants can be explained by the uncovering of an open state that is not detectable in the wild type, is accessed from deep closed states, and reflects an intermediate step along the chain of events leading to channel opening. This allowed us to study gating steps prior to opening, which, for example, explain the mechanism of gating inhibition by Ca2+-Calmodulin, and generate a gating model that describes the characteristic features ofKCNHchannels' gating.

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Section: A Two-layer Markov Model Recapitulates the Kinetic Features ...mentioning

confidence: 99%

Revealing a hidden conducting state by manipulating the intracellular domains in K_V10.1 exposes the coupling between two gating mechanisms

Abdelaziz

Tomczak

Neef³

et al. 2023

Preprint

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“…Several prokaryotic sodium channels structure has been obtained by X-ray crystallography from different bacteria which has allowed to visualize them in the different functional conformations such as inactive (closed) or active (open) channel [19,28,29,34]. These channels, in contrast to eukaryotic channels, are true tetrameric structures, composed of four identical subunits, each one equivalent to a single eukaryotic region on Na v s [34].…”

Section: Introductionmentioning

confidence: 99%

Energy calculations for sodium vs potassium on a prokaryotic voltage-gated sodium channel: a quantum study.

Ferrer,

Fabian

2024

Preprint

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The selectivity of the sodium channel has been the subject of numerous exper- imental and theoretical studies. In this work we address this problem from a theoretical point of view, based on a model built from the selectivity filter (SF) of the open structure of the voltage-activated channel of the bacterium Mag- netococcus marinus. This approach has allowed us to calculate the interaction energies of the system (cation-water-SF-fragment), both for the sodium cation and the potassium cation. The results obtained have highlighted the importance of differential dehydration of cations, as well as the environment where it occurs. Semi-empirical and ab initio methods have been applied to analyze and quantify the interaction energies when the cations are in the SF of the sodium channel, with the DFT (ab initio) methods being those that have given us the key to the distribution of the interaction energies and therefore how dehydration occurs.

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“…state model proposed.A two-layer Markov-Model depicting possible conformations for the sensor and the ring. The sensor in each subunit can independently adopt one of three conformations (up, middle, and down)(Han et al, 2023 ). The up conformation represents the active conformation.…”

mentioning

confidence: 99%

Revealing a hidden conducting state by manipulating the intracellular domains in KV10.1 exposes the coupling between two gating mechanisms

Abdelaziz,

Tomczak,

Neef

et al. 2024

Preprint

View full text Add to dashboard Cite

The KCNH family of potassium channels serves relevant physiological functions in both excitable and non-excitable cells, reflected in the massive consequences of mutations or pharmacological manipulation of their function. This group of channels shares structural homology with other voltage-gated K+ channels. Still, the mechanisms of gating in this family show significant differences with respect to the canonical electromechanical coupling in these molecules. In particular, the large intracellular domains of KCNH channels play a crucial role in gating that is still only partly understood. Using KCNH1(KV10.1) as a model, we have characterized the behavior of a series of modified channels that the current models could not explain. With electrophysiological and biochemical methods combined with mathematical modeling, we show that the behavior of the mutants can be explained by the uncovering of an open state that is not detectable in the wild type, is accessed from deep closed states, and reflects an intermediate step along the chain of events leading to channel opening. This allowed us to study gating steps prior to opening, which, for example, explain the mechanism of gating inhibition by Ca2+-Calmodulin, and generate a gating model that describes the characteristic features of KCNH channels gating.

show abstract

Voltage sensor dynamics of a bacterial voltage-gated sodium channel NavAb reveal three conformational states

Cited by 5 publications

References 32 publications

Revealing a hidden conducting state by manipulating the intracellular domains in K_V10.1 exposes the coupling between two gating mechanisms

Revealing a hidden conducting state by manipulating the intracellular domains in K_V10.1 exposes the coupling between two gating mechanisms

Energy calculations for sodium vs potassium on a prokaryotic voltage-gated sodium channel: a quantum study.

Revealing a hidden conducting state by manipulating the intracellular domains in KV10.1 exposes the coupling between two gating mechanisms

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