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Ion permeation mechanism of the potassium channel

Nature volume 404, pages 881–884 (2000)Cite this article

Abstract

Ion-selective channels enable the specific permeation of ions through cell membranes and provide the basis of several important biological functions; for example, electric signalling in the nervous system1. Although a large amount of electrophysiological data is available1,2, the molecular mechanisms by which these channels can mediate ion transport remain a significant unsolved problem. With the recently determined crystal structure of the representative K+ channel (KcsA) from Streptomyces lividans3, it becomes possible to examine ion conduction pathways on a microscopic level. K+ channels utilize multi-ion conduction mechanisms1,2,4,5,6, and the three-dimensional structure also shows several ions present in the channel. Here we report results from molecular dynamics free energy perturbation calculations that both establish the nature of the multiple ion conduction mechanism and yield the correct ion selectivity of the channel. By evaluating the energetics of all relevant occupancy states of the selectivity filter, we find that the favoured conduction pathway involves transitions only between two main states with a free difference of about 5 kcal mol-1. Other putative permeation pathways can be excluded because they would involve states that are too high in energy.

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Figure 1: View of the solvated KcsA channel in which one of the four subunits has been omitted from the picture to make the pore visible.
Figure 2: The different possible loading states of the four-site selectivity filter.
Figure 3: Free energy profile (potential of mean force) for the single-file movement between the 1010(1) and 0101(1) states.

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Acknowledgements

We thank T. A. Jones for comments and M. R. Harris for graphics. This work was supported by the Wenner–Gren Foundation and the Swedish Natural Science Research Council (NFR).

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, Uppsala, SE-751 24, Sweden

    Johan Åqvist & Victor Luzhkov

  2. Institute of Chemical Physics Problems, Russian Academy of Sciences, Chernogolovka, 142432, Moscow Region, Russian Federation

    Victor Luzhkov

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  1. Johan Åqvist
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  2. Victor Luzhkov
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Correspondence to Johan Åqvist.

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Åqvist, J., Luzhkov, V. Ion permeation mechanism of the potassium channel. Nature 404, 881–884 (2000). https://doi.org/10.1038/35009114

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