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Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels

Kopec, W., Koepfer, D. A., Vickery, O. N., Bondarenko, A. S., Jansen, T. L. C., de Groot, B. L. & Zachariae, U., 20-Jul-2018, In : Nature Chemistry. 10, 8, p. 813-820 8 p.

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  • Direct knock-on of desolvated ions governs strict ion selectivity in K + channels

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DOI

  • Wojciech Kopec
  • David A. Koepfer
  • Owen N. Vickery
  • Anna S. Bondarenko
  • Thomas L. C. Jansen
  • Bert L. de Groot
  • Ulrich Zachariae

The seeming contradiction that K+ channels conduct K+ ions at maximal throughput rates while not permeating slightly smaller Na+ ions has perplexed scientists for decades. Although numerous models have addressed selective permeation in K(+ )channels, the combination of conduction efficiency and ion selectivity has not yet been linked through a unified functional model. Here, we investigate the mechanism of ion selectivity through atomistic simulations totalling more than 400 mu s in length, which include over 7,000 permeation events. Together with free-energy calculations, our simulations show that both rapid permeation of K+ and ion selectivity are ultimately based on a single principle: the direct knock-on of completely desolvated ions in the channels' selectivity filter. Herein, the strong interactions between multiple 'naked' ions in the four filter binding sites give rise to a natural exclusion of any competing ions. Our results are in excellent agreement with experimental selectivity data, measured ion interaction energies and recent two-dimensional infrared spectra of filter ion configurations.

Original languageEnglish
Pages (from-to)813-820
Number of pages8
JournalNature Chemistry
Volume10
Issue number8
Publication statusPublished - 20-Jul-2018

    Keywords

  • FREE-ENERGY LANDSCAPES, POTASSIUM CHANNELS, NAK CHANNEL, BINDING-SITES, KCSA CHANNEL, COMPUTATIONAL ELECTROPHYSIOLOGY, MOLECULAR SIMULATION, PERMEATION, CONDUCTION, MECHANISM

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