Abstract
The nicotinic acetylcholine receptor belongs to a class of molecules that respond transiently to chemical stimuli by opening a water-filled channel through the cell membrane for cations to diffuse. This channel lies along the central axis delineated by a ring of five homologous, membrane-spanning subunits1,2 and thus has properties, such as conductance and ion selectivity, which depend on the profile created by the encircling subunits. Insight has been gained recently about the amino-acid residues implicated directly in the ion transport3–7, and some information about the subunit configuration around the channel has come from electron micros-copy studies of postsynaptic membranes crystallized in the form of flattened tubular vesicles8–11. The resolution along the axis of the channel has, however, been limited by the restricted range of views obtainable. Here we report the structure of the channel at 17 Å resolution, determined by three-dimensional image recon-struction from tubular vesicles having receptors organized in helical arrays across their surfaces. The helical symmetry is preserved by suspending the tubes in thin films of ice, and the receptors in such tubes can be seen from all angles, allowing the channel to be revealed clearly in relation to the lipid bilayer and the peripheral protein for the first time.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Karlin, A. in The Cell Surface and Neuronal Function (eds Cotman, C. W., Poste, G. & Nicolson, G. L.) 191–260 (North-Holland, Amsterdam, 1980).
Changeux, J.-P., Devillers-Thiery, A. & Chemouille, P. Science 225, 1335–1345 (1984).
Giraudat, J. et al. Biochemistry 26, 2410–2418 (1987).
Hucho, F. W., Oberthur, W. & Lottspeich, F. FEBS Lett. 205, 137–142 (1986).
Sakmann, B. et al. Nature 318, 538–543 (1985).
Imoto, K. et al. Nature 324, 670–674 (1986).
Mishina, M. et al. Nature 313, 364–369 (1985).
Brisson, A. & Unwin, P. N. T. J. Cell Biol. 99, 1202–1211 (1984).
Brisson, A. & Unwin, P. N. T. Nature 315, 474–477 (1985).
Kubalek, E. et al. J. Cell Biol. 105, 9–18 (1987).
Unwin, P. N. T., Toyoshima, C. & Kubalek, E. J. Cell Biol. 107, 1123–1138 (1988).
Sealock, R. J. Cell Biol. 92, 514–522 (1982).
Sealock, R., Wray, B. E. & Froehner, S. C. J. Cell Biol. 98, 2239–2244 (1984).
Sobel, A. et al. Proc. natn. Acad. Sci. U.S.A. 75, 510–514 (1978).
LaRochelle, W. J. & Froehner, S. C. J. biol. Chem. 261, 5271–5274 (1986).
Carr, C., McCourt, D. & Cohen, J. B. Biochemistry 26, 7090–7102 (1987).
Barrantes, F. J. J. Cell Biol. 92, 60–68 (1982).
Neubig, R. R. et al. Proc. natn. Acad. Sci. U.S.A. 76, 690–694 (1979).
Toyoshima, C. & Unwin, P. N. T. Ultramicroscopy 25, 279–292 (1988).
Caspar, D. L. D. & Kirschner, D. A. Nature new Biol. 231, 46–52 (1971).
Lepault, J., Pattus, F. & Martin, N. Biochim. biophys. Acta 820, 315–318 (1985).
International Tables for X-ray Crystallography Vol. 3 (Reidel, Holland, 1983).
Popot, J.-L. et al. Eur. J. Biochem. 85, 27–42 (1978).
Bridgman, P. et al. J. Cell. Biol. 105, 1829–1846 (1987).
Porter, S. & Froehner, S. C. J. biol. Chem. 258, 10034–10040 (1983).
Froehner, S. C. Trends Neurosci. 9, 37–41 (1986).
Hille, B. Ionic Channels of Excitable Membranes (Sinauer, Sunderland, 1984).
Dani, J. A. & Eisenman, G. J. gen. Physiol. 89, 959–983 (1987).
DeRosier, D. J. & Moore, P. B. J. molec. Biol. 52, 355–369 (1970).
Popot, J.-L. & Changeux, J.-P. Physiol. Rev. 64, 1162–1239 (1984).
Bonini, I. C. et al. Biochem. J. 245, 111–118 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Toyoshima, C., Unwin, N. Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature 336, 247–250 (1988). https://doi.org/10.1038/336247a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/336247a0
This article is cited by
-
A General Channel Model Accounts for Channel, Carrier, Countertransport and Cotransport Kinetics
Journal of Membrane Biology (2005)
-
Structure and gating mechanism of the acetylcholine receptor pore
Nature (2003)
-
Three-dimensional structure of bovine cytochrome bC1 complex by electron cryomicroscopy and helical image reconstruction
Nature Structural & Molecular Biology (1996)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.