The voltage-dependent gate in MthK potassium channels is located at the selectivity filter

Nat Struct Mol Biol. 2013 Feb;20(2):159-66. doi: 10.1038/nsmb.2473. Epub 2012 Dec 23.


Understanding how ion channels open and close their pores is crucial for comprehending their physiological roles. We used intracellular quaternary ammonium blockers, electrophysiology and X-ray crystallography to locate the voltage-dependent gate in MthK potassium channels from Methanobacterium thermoautotrophicum. Blockers bind in an aqueous cavity between two putative gates: an intracellular gate and the selectivity filter. Thus, these blockers directly probe gate location--an intracellular gate will prevent binding when closed, whereas a selectivity filter gate will always allow binding. Kinetic analysis of tetrabutylammonium block of single MthK channels combined with X-ray crystallographic analysis of the pore with tetrabutyl antimony unequivocally determined that the voltage-dependent gate, like the C-type inactivation gate in eukaryotic channels, is located at the selectivity filter. State-dependent binding kinetics suggest that MthK inactivation leads to conformational changes within the cavity and intracellular pore entrance.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • Ion Channel Gating / physiology*
  • Kinetics
  • Methanobacterium / metabolism*
  • Models, Molecular*
  • Potassium Channels, Voltage-Gated / chemistry*
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Conformation*
  • Quaternary Ammonium Compounds


  • Potassium Channels, Voltage-Gated
  • Quaternary Ammonium Compounds
  • tetrabutylammonium

Associated data

  • PDB/4HYO
  • PDB/4HZ3