Journal article
Disruption of an intersubunit interaction underlies Ca2+-calmodulin modulation of cyclic nucleotide-gated channels
The Journal of neuroscience, Vol.23(22), pp.8167-8175
09/03/2003
Handle:
https://hdl.handle.net/2376/115372
PMID: 12954880
Abstract
Cyclic nucleotide-gated channels are key molecular elements for olfactory transduction. Olfactory adaptation caused by repeated exposure to an odorant has been proposed to be mediated by the binding of Ca2+-calmodulin to the NH2-terminal domain of the channel, breaking its interaction with the COOH-terminal domain and downregulating the channel. We used a fluorescence resonance energy transfer (FRET) approach to study the structural aspects of this domain-domain interaction under physiological conditions in real time. Fluorescent proteins enhanced cyan fluorescent protein and enhanced yellow fluorescent protein were genetically attached at sites adjacent to the NH2- and COOH-terminal interacting domains, respectively, allowing direct observation of molecular rearrangements in intact channels. FRET signals caused by the specific interdomain interaction were observed in both intact cells and excised patches. Comparison of the effective FRET efficiencies demonstrated that the interaction occurs specifically between subunits but not within the same subunit. Binding of Ca2+-calmodulin caused a reversible decrease in FRET with the same time course as channel downregulation. These results suggest that a separation or reorientation of the interacting domains between subunits by Ca2+-calmodulin leads to channel downregulation. The quaternary arrangement presents a structural framework for understanding the molecular mechanism of olfactory adaptation.
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Details
- Title
- Disruption of an intersubunit interaction underlies Ca2+-calmodulin modulation of cyclic nucleotide-gated channels
- Creators
- Jie Zheng - Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195-7290, USAMichael D VarnumWilliam N Zagotta
- Publication Details
- The Journal of neuroscience, Vol.23(22), pp.8167-8175
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- United States
- Grant note
- R01 EY010329-10 / NEI NIH HHS R01 EY010329 / NEI NIH HHS EY10329 / NEI NIH HHS
- Identifiers
- 99900547715201842
- Language
- English
- Resource Type
- Journal article