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

Nat Chem. 2018 Aug;10(8):813-820. doi: 10.1038/s41557-018-0105-9. Epub 2018 Jul 20.

Abstract

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 μs 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations, Monovalent / chemistry*
  • Cations, Monovalent / metabolism*
  • Ion Transport
  • Potassium / chemistry*
  • Potassium / metabolism*
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Sodium / chemistry
  • Sodium / metabolism
  • Spectrophotometry, Infrared
  • Substrate Specificity

Substances

  • Cations, Monovalent
  • Potassium Channels
  • Sodium
  • Potassium