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Rotational movement during cyclic nucleotide-gated channel opening

Nature volume 412, pages 917–921 (2001)Cite this article

Abstract

Cyclic nucleotide-gated (CNG) channels are crucial components of visual, olfactory and gustatory signalling pathways. They open in response to direct binding of intracellular cyclic nucleotides and thus contribute to cellular control of both the membrane potential and intracellular Ca2+ levels1. Cytosolic Ni2+ potentiates the rod channel (CNG1) response to cyclic nucleotides2,3,4 and inhibits the olfactory channel (CNG2) response5. Modulation is due to coordination of Ni2+ by channel-specific histidines in the C-linker, between the S6 transmembrane segment and the cyclic nucleotide-binding domain. Here we report, using a histidine scan of the initial C-linker of the CNG1 channel, stripes of sites producing Ni2+ potentiation or Ni2+ inhibition, separated by 50° on an α-helix. These results suggest a model for channel gating where rotation of the post-S6 region around the channel's central axis realigns the Ni2+-coordinating residues of multiple subunits. This rotation probably initiates movement of the S6 and pore opening.

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Figure 1: Ni2+-coordinating histidines. a, Sequence alignment showing the location of Ni2+-coordinating histidines in CNG1 and CNG2.
Figure 2: Ni2+-histidine modulation.
Figure 3: Energetic effects of Ni2+.
Figure 4: L values calculated from saturating cyclic nucleotide concentrations.
Figure 5: Models showing how Ni2+ coordination could change CNG1 gating.

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Acknowledgements

We would like to thank K. D. Black, G. Sheridan and especially H. Utsugi for technical assistance. We also thank A. D. Bragg, K. Craven, G. E. Flynn, K. Matulef, M. C. Trudeau and J. Zheng for their insightful discussions and critical reading of the manuscript.

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  1. Howard Hughes Medical Institute & Department of Physiology and Biophysics, Box 357290, University of Washington School of Medicine, Seattle, 98195, Washington, USA

    J. P. Johnson Jr & William N. Zagotta

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Correspondence to William N. Zagotta.

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Johnson, J., Zagotta, W. Rotational movement during cyclic nucleotide-gated channel opening. Nature 412, 917–921 (2001). https://doi.org/10.1038/35091089

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