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Voltage-dependent gating at the KcsA selectivity filter

Nature Structural & Molecular Biology volume 13, pages 319–322 (2006)Cite this article

Abstract

The prokaryotic K+ channel KcsA, although lacking a 'standard' voltage-sensing domain, shows voltage-dependent gating that leads to an increase in steady-state open probability of almost two orders of magnitude between +150 and −150 mV. Here we show that voltage-dependent gating in KcsA is associated with the movement of ∼0.7 equivalent electronic charges. This charge movement produces an increase in the rate of entry into a long-lived inactivated state and seems to be independent of the proton-activation mechanism. Charge neutralization at position 71 renders the channel essentially voltage-independent by preventing entry into the inactivated state. A mechanism for voltage-dependent gating at the selectivity filter is proposed that is based on the reorientation of the carboxylic moiety of Glu71 and its influence in the conformational dynamics of the selectivity filter.

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Figure 1: KcsA gating is modulated by transmembrane voltage.
Figure 2: Voltage gating is independent of proton-dependent gating.
Figure 3: The voltage sensor in KcsA is located at the selectivity filter.
Figure 4: Neutralizing Glu71 sharply reduces its voltage dependence.

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Acknowledgements

We thank B. Roux for illuminating discussions and for critically reading the manuscript and S. Chakrapani, C. Ptak, D.M. Cortes and V. Vasquez for useful discussions and advice. This work was supported by grants from the US National Institutes of Health to E.P.

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Author notes

  1. Luis G Cuello & Eduardo Perozo

    Present address: Institute of Molecular Pediatrics Science and Department of Biochemistry and Molecular Biology, University of Chicago, Pritzker School of Medicine, 929 E 57th Street, W206, Chicago, Illinois, 60637, USA

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  1. Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, 22906, Virginia, USA

    Julio F Cordero-Morales, Luis G Cuello & Eduardo Perozo

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  1. Julio F Cordero-Morales
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Correspondence to Eduardo Perozo.

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Cordero-Morales, J., Cuello, L. & Perozo, E. Voltage-dependent gating at the KcsA selectivity filter. Nat Struct Mol Biol 13, 319–322 (2006). https://doi.org/10.1038/nsmb1070

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