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

João H. Morais-Cabral, Yufeng Zhou and Roderick MacKinnon ()
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João H. Morais-Cabral: Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University
Yufeng Zhou: Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University
Roderick MacKinnon: Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University

Nature, 2001, vol. 414, issue 6859, 37-42

Abstract: 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.

Date: 2001
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DOI: 10.1038/35102000

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