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Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution

Nature volume 414, pages 43–48 (2001)Cite this article

Abstract

Ion transport proteins must remove an ion's hydration shell to coordinate the ion selectively on the basis of its size and charge. To discover how the K+ channel solves this fundamental aspect of ion conduction, we solved the structure of the KcsA K+ channel in complex with a monoclonal Fab antibody fragment at 2.0 Å resolution. Here we show how the K+ channel displaces water molecules around an ion at its extracellular entryway, and how it holds a K+ ion in a square antiprism of water molecules in a cavity near its intracellular entryway. Carbonyl oxygen atoms within the selectivity filter form a very similar square antiprism around each K+ binding site, as if to mimic the waters of hydration. The selectivity filter changes its ion coordination structure in low K+ solutions. This structural change is crucial to the operation of the selectivity filter in the cellular context, where the K+ ion concentration near the selectivity filter varies in response to channel gating.

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Figure 1: Fab attachment and crystal packing.
Figure 2: Stereo view of electron density in the region of the K+ channel selectivity filter.
Figure 3: Stereo view of a hydrated K+ ion in the central cavity.
Figure 4: Potassium ion dehydration at the extracellular pore entryway.
Figure 5: High- and low-K+ structures of the selectivity filter (stereo views).
Figure 6: Biological significance of the K+-dependent structural change in the selectivity filter.

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Acknowledgements

We thank the staff at the National Synchrotron Light Source X-25 and Cornell High Energy Synchrotron Source A1 and F1 for assistance, Y. Jiang for help and advice at many stages of this project, F. Weis-Garcia and M. Nussenzweig for advice and teaching monoclonal methods, R. Dutzler for lipid topology files, and F. Valiyaveetil and J. Dunitz for discussions. This project was supported by a grant from the National Institutes of Health to R.M. R.M. is an investigator in the Howard Hughes Medical Institute.

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  1. João H. Morais-Cabral

    Present address: Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut, 06520, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Yufeng Zhou, João H. Morais-Cabral, Amelia Kaufman & Roderick MacKinnon

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Zhou, Y., Morais-Cabral, J., Kaufman, A. et al. Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution. Nature 414, 43–48 (2001). https://doi.org/10.1038/35102009

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