Change of pore helix conformational state upon opening of cyclic nucleotide-gated channels

Neuron. 2000 Dec;28(3):899-909. doi: 10.1016/s0896-6273(00)00162-8.


The structure of the pore region of the alpha subunit of the bovine rod cyclic nucleotide-gated channel was probed using cysteine-scanning mutagenesis and hydrophilic sulfhydryl-reactive methanethiosulfonate (MTS) reagents. A region homologous to the pore helix in the X-ray crystal structure of the KcsA K(+) channel showed a helical pattern of reactivity with externally applied MTS reagents. Surprisingly, three out of four of the reactive residues, all on one face of the pore helix, only reacted with MTS reagents in the closed state. A residue on the opposite face of the helix only reacted with MTS reagents in the open state. These results indicate that the pore helix (or its surroundings) undergoes a change in conformation, perhaps involving a rotation around its long axis, that opens a gate localized to the selectivity filter of the channel.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins*
  • Cattle
  • Cells, Cultured
  • Cyclic Nucleotide-Gated Cation Channels
  • Ethyl Methanesulfonate / analogs & derivatives
  • Ethyl Methanesulfonate / pharmacology
  • Indicators and Reagents
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Ion Channels / genetics*
  • Ion Channels / metabolism*
  • Mesylates / pharmacology
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Oocytes / cytology
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels / genetics
  • Protein Conformation / drug effects
  • Protein Structure, Secondary / drug effects
  • Protein Structure, Secondary / physiology
  • Retinal Rod Photoreceptor Cells / metabolism
  • Sequence Homology, Amino Acid
  • Sulfhydryl Reagents / pharmacology
  • Water / metabolism
  • Xenopus


  • Bacterial Proteins
  • Cyclic Nucleotide-Gated Cation Channels
  • Indicators and Reagents
  • Ion Channels
  • Mesylates
  • Potassium Channels
  • Sulfhydryl Reagents
  • methanethiosulfonate ethylammonium
  • prokaryotic potassium channel
  • Water
  • (2-(trimethylammonium)ethyl)methanethiosulfonate
  • methanethiosulfonate
  • Ethyl Methanesulfonate