SHEN Rong and GUO Wanlin. Mechanism for Variable Selectivity and Conductance in Mutated NaK Channels. Journal of Physical Chemistry Letters 2012, 3, 2887-2891.

Mechanism for Variable Selectivity and Conductance in Mutated NaK Channels

Rong Shen and Wanlin Guo
Institute of Nano Science, State Key Laboratory of Mechanics and Control for Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China

J. Phys. Chem. Lett., 2012, 3 (19), pp 2887–2891
DOI: 10.1021/jz301225d
Publication Date (Web): September 20, 2012

Abstract

Na+ conduction has been demonstrated in a few K+ channels and has been widely used to characterize the physiological selectivity and C-type inactivation in K+ channels. By using molecular dynamics simulations and free-energy calculations, we found that K+ and Na+ have distinct preferable binding configurations in the conductive filter of two highly K+ selective channels, which are mutated from the nonselective NaK channel and can conduct Na+ upon removal of K+. Disruption of a conserved hydrogen bond interaction between residues in the filter and the pore helices can significantly decrease the free-energy differences and barriers between the K+ binding configurations, whereas it has little effect on the free-energy landscape for Na+. We propose that the enhancement of the fluctuation of the filter structure decreases the affinity and conducting barrier of K+ and therefore the ability of K+ to block Na+ currents, predominantly responsible for the reduced K+ selectivity.

Keywords: NaK channel; mutation; ion selectivity; ion conductance; hydrogen bond; molecular dynamics simulation

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