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Energetic optimization of ion conduction rate by the K+ selectivity filter

Nature volume 414, pages 37–42 (2001)Cite this article

Abstract

The K+ selectivity filter catalyses the dehydration, transfer and rehydration of a K+ ion in about ten nanoseconds. This physical process is central to the production of electrical signals in biology. Here we show how nearly diffusion-limited rates are achieved, by analysing ion conduction and the corresponding crystallographic ion distribution in the selectivity filter of the KcsA K+ channel. Measurements with K+ and its slightly larger analogue, Rb+, lead us to conclude that the selectivity filter usually contains two K+ ions separated by one water molecule. The two ions move in a concerted fashion between two configurations, K+-water-K+-water (1,3 configuration) and water-K+-water-K+ (2,4 configuration), until a third ion enters, displacing the ion on the opposite side of the queue. For K+, the energy difference between the 1,3 and 2,4 configurations is close to zero, the condition of maximum conduction rate. The energetic balance between these configurations is a clear example of evolutionary optimization of protein function.

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Figure 1: Binding sites for K+ ions in the KcsA K+ channel.
Figure 2: Rubidium conduction and crystallographic distribution of Rb+ ions in the selectivity filter.
Figure 3: Potassium conduction and crystallographic distribution of K+ ions in the selectivity filter.
Figure 4: Analysis of a conduction-state diagram constructed on the basis of the electron density profiles.
Figure 5: The biologically important throughput cycle for K+ ions.
Figure 6: Energetic optimization of K+ ion conduction.

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Acknowledgements

We thank, for assistance, the staff at the National Synchrotron Light Source X-25; at Cornell High Energy Synchrotron Source, A1 and F1; at the Advanced Photon Source, ID19; and at the European Synchrotron Radiation Source, ID13. We thank Y. Jiang, R. Dutzler and A. Pico for assistance in data collection; B. Roux for discussions; and F. Valiyaveetil for discussion and advice on the manuscript. This work 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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Author notes

  1. João H. Morais-Cabral

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

  2. Roderick MacKinnon: Correspondence and requests for materials should be addressed to R.M. Coordinates have been deposited with the Protein Data Bank under accession codes 1JVM, 1K4C and 1K4D.

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

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

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Morais-Cabral, J., Zhou, Y. & MacKinnon, R. Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 414, 37–42 (2001). https://doi.org/10.1038/35102000

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