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Science 3 October 1997:
Vol. 278. no. 5335, pp. 110 - 113
DOI: 10.1126/science.278.5335.110
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Reports

Interdomain Interactions Underlying Activation of Cyclic Nucleotide-Gated Channels

Michael D. Varnum, William N. Zagotta *

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.

Department of Physiology and Biophysics, and Howard Hughes Medical Institute, Box 357370, University of Washington School of Medicine, Seattle, WA 98195, USA.
*   To whom correspondence should be addressed. E-mail: zagotta{at}u.washington.edu

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