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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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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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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