title: Interdomain interactions underlying activation of cyclic nucleotide-gated channels.
abstract: Cyclic nucleotide-gated (CNG) ion channels are multimeric proteins that activate in response to the binding of cyclic nucleotide to intracellular domains. Here, an intramolecular protein-protein interaction between the amino-terminal domain and the carboxyl-terminal ligand-binding domain of the rat olfactory CNG channel was shown to exert an autoexcitatory effect on channel activation. Calcium-calmodulin, which modulates CNG channel activity during odorant adaptation, blocked this interaction. A specific deletion within the amino-terminal domain disrupted the interdomain interaction in vitro and altered the gating properties and calmodulin sensitivity of expressed channels. Thus, the amino-terminal domain may promote channel opening by directly interacting with the carboxyl-terminal gating machinery; calmodulin regulates channel activity by targeting this interaction.
authors.affiliation: Department of Physiology and Biophysics, and Howard Hughes Medical Institute, Box 357370, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Varnum
authors.forename: W N
authors.initials: WN
authors.lastname: Zagotta
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D008024:Ligands; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D014981:Xenopus
chemical_list: D002147:Calmodulin; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D008024:Ligands; D011993:Recombinant Fusion Proteins; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium