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Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel

Nature Neuroscience volume 6, pages 353–361 (2003)Cite this article

Abstract

MVP, a Methanococcus jannaschii voltage-gated potassium channel, was cloned and shown to operate in eukaryotic and prokaryotic cells. Like pacemaker channels, MVP opens on hyperpolarization using S4 voltage sensors like those in classical channels activated by depolarization. The MVP S4 span resembles classical sensors in sequence, charge, topology and movement, traveling inward on hyperpolarization and outward on depolarization (via canaliculi in the protein that bring the extracellular and internal solutions into proximity across a short barrier). Thus, MVP opens with sensors inward indicating a reversal of S4 position and pore state compared to classical channels. Homolo-gous channels in mammals and plants are expected to function similarly.

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Figure 1: Amino acid sequence and predicted topology of MVP.
Figure 2: MVP rescues yeast and bacterial cells and yields potassium currents.
Figure 3: MVP currents: activation and selectivity.
Figure 4: Single MVP channels are opened by hyperpolarization.
Figure 5: The MVP S4 is upright in the membrane.
Figure 6: Modification of sentinel cysteines in S4 is side and voltage-dependent.
Figure 7: Modification of sentinel cysteines in S4 is state-dependent.

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Protein Data Bank

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Acknowledgements

This work was supported by grants to S.A.N.G. from the National Institutes of Health. S.A.N.G. is a Doris Duke Charitable Foundation Distinguished Clinical Scholar Award recipient. We thank R. Goldstein for technical and lexical support.

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Author notes

  1. Federico Sesti

    Present address: Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey, 08854, USA

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  1. Departments of Pediatrics and Cellular and Molecular Physiology, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536, Connecticut, USA

    Federico Sesti, Sindhu Rajan, Rosana Gonzalez-Colaso, Natalia Nikolaeva & Steve A.N. Goldstein

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Sesti, F., Rajan, S., Gonzalez-Colaso, R. et al. Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel. Nat Neurosci 6, 353–361 (2003). https://doi.org/10.1038/nn1028

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