Pore hydration states of KcsA potassium channels in membranes

J Biol Chem. 2015 Oct 30;290(44):26765-75. doi: 10.1074/jbc.M115.661819. Epub 2015 Sep 14.


Water-filled hydrophobic cavities in channel proteins serve as gateways for transfer of ions across membranes, but their properties are largely unknown. We determined water distributions along the conduction pores in two tetrameric channels embedded in lipid bilayers using neutron diffraction: potassium channel KcsA and the transmembrane domain of M2 protein of influenza A virus. For the KcsA channel in the closed state, the distribution of water is peaked in the middle of the membrane, showing water in the central cavity adjacent to the selectivity filter. This water is displaced by the channel blocker tetrabutyl-ammonium. The amount of water associated with the channel was quantified, using neutron diffraction and solid state NMR. In contrast, the M2 proton channel shows a V-shaped water profile across the membrane, with a narrow constriction at the center, like the hourglass shape of its internal surface. These two types of water distribution are therefore very different in their connectivity to the bulk water. The water and protein profiles determined here provide important evidence concerning conformation and hydration of channels in membranes and the potential role of pore hydration in channel gating.

Keywords: KcsA; M2; influenza virus; ion channels; lipid bilayer; neutron diffraction; nuclear magnetic resonance (NMR); potassium channel.

Publication types

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

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Influenza A virus / chemistry
  • Influenza A virus / metabolism
  • Ion Channel Gating
  • Ion Transport
  • Lipid Bilayers / chemistry
  • Models, Molecular
  • Phosphatidylcholines / chemistry
  • Phosphatidylglycerols / chemistry
  • Potassium / chemistry*
  • Potassium / metabolism
  • Potassium Channel Blockers / chemistry
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Protein Conformation
  • Protein Multimerization
  • Protons*
  • Quaternary Ammonium Compounds / chemistry
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Streptomyces lividans / chemistry
  • Streptomyces lividans / metabolism
  • Viral Matrix Proteins / chemistry*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism
  • Water / chemistry*
  • Water / metabolism


  • Bacterial Proteins
  • Lipid Bilayers
  • M2 protein, Influenza A virus
  • Phosphatidylcholines
  • Phosphatidylglycerols
  • Potassium Channel Blockers
  • Potassium Channels
  • Protons
  • Quaternary Ammonium Compounds
  • Recombinant Proteins
  • Viral Matrix Proteins
  • prokaryotic potassium channel
  • Water
  • 1-palmitoyl-2-oleoylglycero-3-phosphoglycerol
  • tetrabutylammonium
  • Potassium
  • 1-palmitoyl-2-oleoylphosphatidylcholine

Associated data

  • PDB/1K4C