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

Simone Furini, Carmen Domene Nunez

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2106-2114
Number of pages9
JournalBiophysical Journal
Volume103
Issue number10
Early online date20 Nov 2012
DOIs
Publication statusPublished - 21 Nov 2012

Keywords

  • KCSA POTASSIUM CHANNEL, MOLECULAR-DYNAMICS SIMULATIONS, ION SELECTIVITY, K+ CHANNEL, POTENTIAL FUNCTIONS, METAL-IONS, PERMEATION, WATER, RESOLUTION, MECHANISM

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