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Science 25 November 1994:
Vol. 266. no. 5189, pp. 1348 - 1354
DOI: 10.1126/science.266.5189.1348
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Articles

Calcium-Calmodulin Modulation of the Olfactory Cyclic Nucleotide-Gated Cation Channel

Mingyao Liu 1, Tsung-Yu Chen 2, Basheer Ahamed 1, Jess Li 1, and King-Wai Yau 3

1 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Although several ion channels have been reported to be directly modulated by calcium-calmodulin, they have not been conclusively shown to bind calmodulin, nor are the modulatory mechanisms understood. Study of the olfactory cyclic nucleotide-activated cation channel, which is modulated by calcium-calmodulin, indicates that calcium-calmodulin directly binds to a specific domain on the amino terminus of the channel. This binding reduces the effective affinity of the channel for cyclic nucleotides, apparently by acting on channel gating, which is tightly coupled to ligand binding. The data reveal a control mechanism that resembles those underlying the regulation of enzymes by calmodulin. The results also point to the amino-terminal part of the olfactory channel as an element for gating, which may have general significance in the operation of ion channels with similar overall structures.

Submitted on July 15, 1994
Accepted on October 26, 1994


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