title: Rotational movement during cyclic nucleotide-gated channel opening.
abstract: Cyclic nucleotide-gated (CNG) channels are crucial components of visual, olfactory and gustatory signalling pathways. They open in response to direct binding of intracellular cyclic nucleotides and thus contribute to cellular control of both the membrane potential and intracellular Ca2+ levels. Cytosolic Ni2+ potentiates the rod channel (CNG1) response to cyclic nucleotides and inhibits the olfactory channel (CNG2) response. Modulation is due to coordination of Ni2+ by channel-specific histidines in the C-linker, between the S6 transmembrane segment and the cyclic nucleotide-binding domain. Here we report, using a histidine scan of the initial C-linker of the CNG1 channel, stripes of sites producing Ni2+ potentiation or Ni2+ inhibition, separated by 50 degrees on an alpha-helix. These results suggest a model for channel gating where rotation of the post-S6 region around the channel's central axis realigns the Ni2+-coordinating residues of multiple subunits. This rotation probably initiates movement of the S6 and pore opening.
authors.affiliation: Howard Hughes Medical Institute & Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Johnson
authors.forename: W N
authors.initials: WN
authors.lastname: Zagotta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006152:Cyclic GMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels; D006639:Histidine / Q000737:chemistry; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D009154:Mutation; D009532:Nickel / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014982:Xenopus laevis
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D011994:Recombinant Proteins; D006639:Histidine; D009532:Nickel; D006152:Cyclic GMP