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Structural analysis of ion selectivity in the NaK channel

Nature Structural & Molecular Biology volume 16, pages 3541 (2009) | Download Citation

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Abstract

Here we present a detailed characterization of ion binding in the NaK pore using the high-resolution structures of NaK in complex with various cations. These structures reveal four ion binding sites with similar chemical environments but vastly different ion preference. The most nonselective of all is site 3, which is formed exclusively by backbone carbonyl oxygen atoms and resides deep within the selectivity filter. Additionally, four water molecules in combination with four backbone carbonyl oxygen atoms are seen to participate in K+ and Rb+ ion chelation, at both the external entrance and the vestibule of the NaK filter, confirming the channel's preference for an octahedral ligand configuration for K+ and Rb+ binding. In contrast, Na+ binding in the NaK filter, particularly at site 4, utilizes a pyramidal ligand configuration that requires the participation of a water molecule in the cavity. Therefore, the ability of the NaK filter to bind both Na+ and K+ ions seemingly arises from the ions' ability to use the existing environment in unique ways, rather than from any structural rearrangements of the filter itself.

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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 Howard Hughes Medical Institute and by grants from the the US National Institutes of Health (NIH) 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 NIH Training Grant T32 GM008297.

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Affiliations

  1. Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9040, USA.

    • Amer Alam
    •  & Youxing Jiang
  2. Howard Hughes Medical Institute, 5901 Forest Park Drive, Dallas, Texas 75390-9050, USA.

    • Youxing Jiang

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Contributions

A.A. performed the research. A.A. & 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.1537

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