Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels

Neuron. 2001 Jun;30(3):689-98. doi: 10.1016/s0896-6273(01)00324-5.


In cyclic nucleotide-gated channels (CNG), direct binding of cyclic nucleotides in the carboxy-terminal region is allosterically coupled to opening of the pore. A CNG1 channel pore was probed using site-directed cysteine substitution to elucidate conformational changes associated with channel opening. The effects of cysteine modification on permeation suggest a structural homology between CNG and KcsA pores. We found that intersubunit disulfide bonds form spontaneously between S399C residues in the helix bundle when channels are in the closed but not in the open state. While MTSET modification of pore-lining residues was state dependent, Ag(+) modification of V391C, in the inner vestibule, occurred at the same diffusion-limited rate in both open and closed states. Our results suggest that the helix bundle undergoes a conformational change associated with gating but is not the activation gate for CNG channels.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins*
  • Cattle
  • Cyclic Nucleotide-Gated Cation Channels
  • Cysteine / genetics
  • Ion Channel Gating / physiology*
  • Ion Channels / chemistry*
  • Ion Channels / genetics*
  • Ion Channels / metabolism
  • Molecular Sequence Data
  • Oocytes / physiology
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Protein Conformation
  • Retinal Rod Photoreceptor Cells / chemistry*
  • Xenopus laevis


  • Bacterial Proteins
  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels
  • Potassium Channels
  • prokaryotic potassium channel
  • Cysteine