Potassium channel selectivity filter dynamics revealed by single-molecule FRET

Nat Chem Biol. 2019 Apr;15(4):377-383. doi: 10.1038/s41589-019-0240-7. Epub 2019 Mar 4.

Abstract

Potassium (K) channels exhibit exquisite selectivity for conduction of K+ ions over other cations, particularly Na+. High-resolution structures reveal an archetypal selectivity filter (SF) conformation in which dehydrated K+ ions, but not Na+ ions, are perfectly coordinated. Using single-molecule FRET (smFRET), we show that the SF-forming loop (SF-loop) in KirBac1.1 transitions between constrained and dilated conformations as a function of ion concentration. The constrained conformation, essential for selective K+ permeability, is stabilized by K+ but not Na+ ions. Mutations that render channels nonselective result in dilated and dynamically unstable conformations, independent of the permeant ion. Further, while wild-type KirBac1.1 channels are K+ selective in physiological conditions, Na+ permeates in the absence of K+. Moreover, whereas K+ gradients preferentially support 86Rb+ fluxes, Na+ gradients preferentially support 22Na+ fluxes. This suggests differential ion selectivity in constrained versus dilated states, potentially providing a structural basis for this anomalous mole fraction effect.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Cell Membrane Permeability / physiology
  • Crystallography, X-Ray / methods
  • Fluorescence Resonance Energy Transfer / methods
  • Humans
  • Ion Channel Gating
  • Models, Molecular
  • Potassium / metabolism
  • Potassium / physiology
  • Potassium Channels / metabolism*
  • Potassium Channels / physiology*
  • Protein Conformation
  • Single Molecule Imaging
  • Sodium / metabolism
  • Structure-Activity Relationship

Substances

  • Potassium Channels
  • Sodium
  • Potassium