The NaK channel is a cation-selective protein with similar permeability for K+ and Na+ ions. Crystallographic structures are available for the wild-type and mutated NaK channels with different numbers of cation-binding sites. We have performed a comparison between the potentials of mean force governing the translocation of K+ ions and mixtures of one Na+ and three K+ ions in a mutated NaK channel with only three cation-binding sites (NaK-CNG). Since NaK-CNG is not selective for K+ over Na+, analysis of its multi-ion potential energy surfaces can provide clues about how selectivity originates. Comparison of the potentials of mean force of NaK-CNG and K+-selective channels yields observations that strongly suggest that the number of contiguous ion binding sites in a single-file mechanism is the key determinant of the channel's selectivity properties, as already proposed by experimental studies. We conclude that the presence of four binding sites in K+-selective channels is essential for highly selective and efficient permeation of K+ ions, and that a key difference between K+-selective and nonselective channels is the absence/presence of a binding site for Na+ ions at the boundary between S2 and S3 in the context of multi-ion permeation events.

Furini, S., Carmen, D. (2012). Nonselective Conduction in a Mutated NaK Channel with Three Cation-Binding Sites. BIOPHYSICAL JOURNAL, 103, 2106-2114 [10.1016/j.bpj.2012.10.004].

Nonselective Conduction in a Mutated NaK Channel with Three Cation-Binding Sites

FURINI, SIMONE;
2012-01-01

Abstract

The NaK channel is a cation-selective protein with similar permeability for K+ and Na+ ions. Crystallographic structures are available for the wild-type and mutated NaK channels with different numbers of cation-binding sites. We have performed a comparison between the potentials of mean force governing the translocation of K+ ions and mixtures of one Na+ and three K+ ions in a mutated NaK channel with only three cation-binding sites (NaK-CNG). Since NaK-CNG is not selective for K+ over Na+, analysis of its multi-ion potential energy surfaces can provide clues about how selectivity originates. Comparison of the potentials of mean force of NaK-CNG and K+-selective channels yields observations that strongly suggest that the number of contiguous ion binding sites in a single-file mechanism is the key determinant of the channel's selectivity properties, as already proposed by experimental studies. We conclude that the presence of four binding sites in K+-selective channels is essential for highly selective and efficient permeation of K+ ions, and that a key difference between K+-selective and nonselective channels is the absence/presence of a binding site for Na+ ions at the boundary between S2 and S3 in the context of multi-ion permeation events.
2012
Furini, S., Carmen, D. (2012). Nonselective Conduction in a Mutated NaK Channel with Three Cation-Binding Sites. BIOPHYSICAL JOURNAL, 103, 2106-2114 [10.1016/j.bpj.2012.10.004].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/43145
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