1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
2. Present address: Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520, USA.

Correspondence to: Roderick MacKinnon Correspondence and requests for materials should be addressed to R.M. (e-mail: Email: mackinn@rockvax.rockefeller.edu). Coordinates have been deposited with the Protein Data Bank under accession codes 1JVM, 1K4C and 1K4D.

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.

1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
2. Present address: Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520, USA.

Correspondence to: Roderick MacKinnon Correspondence and requests for materials should be addressed to R.M. (e-mail: Email: mackinn@rockvax.rockefeller.edu). Coordinates have been deposited with the Protein Data Bank under accession codes 1JVM, 1K4C and 1K4D.