INTERDOMAIN INTERACTIONS UNDERLYING ACTIVATION OF CYCLIC NUCLEOTIDE-GATED CHANNELS

Cyclic nucleotide-gated (CNG) ion channels are multimeric proteins tha t activate in response to the binding of cyclic nucleotide to intracel lular domains. Here, an intramolecular protein-protein interaction bet ween the amino-terminal domain and the carboxylterminal ligand-binding domain of the rat olfactory CNG channel was shown to exert an autoexc itatory effect on channel activation. Calcium-calmodulin, which modula tes CNG channel activity during odorant adaptation, blocked this inter action. A specific deletion within the amino-terminal domain disrupted the interdomain interaction in vitro and altered the gating propertie s and calmodulin sensitivity of expressed channels. Thus, the amino-te rminal domain may promote channel opening by directly interacting with the carboxyl-terminal gating machinery; calmodulin regulates channel activity by targeting this interaction.