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High-resolution structure of the open NaK channel

Nature Structural & Molecular Biology volume 16, pages 3034 (2009) | Download Citation

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Abstract

We report the crystal structure of the nonselective cation channel NaK from Bacillus cereus at a resolution of 1.6 Å. The structure reveals the intracellular gate in an open state, as opposed to the closed form reported previously, making NaK the only channel for which the three-dimensional structures of both conformations are known. Channel opening follows a conserved mechanism of inner helix bending using a flexible glycine residue, the gating hinge, seen in MthK and most other tetrameric cation channels. Additionally, distinct inter and intrasubunit rearrangements involved in channel gating are seen and characterized for the first time along with inner helix twisting motions. Furthermore, we identify a residue deeper within the cavity of the channel pore, Phe92, which is likely to form a constriction point within the open pore, restricting ion flux through the channel. Mutating this residue to alanine causes a subsequent increase in ion-conduction rates as measured by 86Rb flux assays. The structures of both the open and closed conformations of the NaK channel correlate well with those of equivalent K+ channel conformations, namely MthK and KcsA, respectively.

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Acknowledgements

Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the US Department of Energy, Office of Energy Research. We thank the beamline staff for assistance in data collection. This work was supported by the Howard Hughes Medical Institute and by grants from the the US National Institutes of Health and National Institute of General Medical Sciences (RO1 GM079179), the David and Lucile Packard Foundation and the McKnight Endowment for Neuroscience. A.A. was supported by National Institutes of Health Training Grant T32 GM008297.

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Affiliations

  1. Howard Hughes Medical Institute, 5901 Forest Park Drive, Dallas, Texas 75390-9050, USA.

    • Youxing Jiang
  2. Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas Dallas, Texas 75390-9040, USA.

    • Amer Alam
    •  & Youxing Jiang

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Contributions

A.A. performed the research; A.A and Y.J designed the research, analyzed data and wrote the manuscript.

Corresponding author

Correspondence to Youxing Jiang.

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https://doi.org/10.1038/nsmb.1531

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