Skip to main content
Log in

Acetylcholine receptor channel imaged in the open state

  • Article
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

The structure of the open-channel form of the acetylcholine receptor has been determined from electron images of Torpedo ray postsynaptic membranes activated by brief (<5ms) mixing with droplets containing acetylcholine. Comparison with the closed-channel form shows that acetylcholine initiates small rotations of the subunits in the extracellular domain, which trigger a change in configuration of α-helices lining the membrane-spanning pore. The open pore tapers towards the intracellular membrane face, where it is shaped by a 'barrel' of α-helices having a pronounced right-handed twist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hille, B. Ionic Channels of Excitable Membranes (Sinauer, Sunderland, 1992).

    Google Scholar 

  2. Lester, H. A. A. Rev. Biophys. biomolec. Struct. 21, 267–292 (1992).

    Article  CAS  Google Scholar 

  3. Karlin, A. Curr. Opin. Neurobiol. 3, 299–309 (1993).

    Article  CAS  Google Scholar 

  4. Changeux, J.-P., Galzi, J.-L., Devillers-Thiery, A. & Bertrand, D. Qt. Rev. Biophys. 25, 395–432 (1992).

    Article  CAS  Google Scholar 

  5. Toyoshima, C. & Unwin, N. Nature 336, 247–250 (1988).

    Article  ADS  CAS  Google Scholar 

  6. Toyoshima, C. & Unwin, P. N. T. J. Cell Biol. 111, 2623–2635 (1990).

    Article  CAS  Google Scholar 

  7. Unwin, N. J. molec. Biol. 229, 1101–1124 (1993).

    Article  CAS  Google Scholar 

  8. Dilger, J. P. & Brett, R. S. Biophys. J. 57, 723–731 (1990).

    Article  ADS  CAS  Google Scholar 

  9. Matsubara, N., Billington, A. P. & Hess, G. P. Biochemistry 31, 5507–5514 (1992).

    Article  CAS  Google Scholar 

  10. Colquhoun, D. & Sakmann, B. J. Physiol. Lond. 369, 501–557 (1985).

    Article  CAS  Google Scholar 

  11. Colquhoun, D. & Ogden, D. C. J. Physiol. Lond. 395, 131–159 (1988).

    Article  CAS  Google Scholar 

  12. Brisson, A. & Unwin, P. N. T. J. Cell Biol. 99, 1202–1211 (1984).

    Article  CAS  Google Scholar 

  13. DeRosier, D. J. & Klug, A. Nature 217, 130–134 (1968).

    Article  ADS  CAS  Google Scholar 

  14. Berriman, J. A. & Unwin, N. Ultramicroscopy 56, 241–252 (1994).

    Article  CAS  Google Scholar 

  15. Herz, J. M., Johnson, D. A. & Taylor, P. J. biol. Chem. 264, 12439–12448 (1989).

    CAS  PubMed  Google Scholar 

  16. Valenzuela, C. F., Weign, P., Yguerabide, J. & Johnson, D. A. Biophys. J. 66, 674–682 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Blount, P. & Merlie, J. P. Neuron 3, 349–357 (1989).

    Article  CAS  Google Scholar 

  18. Pedersen, S. E. & Cohen, J. B. Proc. natn. Acad. Sci. U.S.A. 87, 2785–2789 (1990).

    Article  ADS  CAS  Google Scholar 

  19. Sine, S. M. & Claudio, T. J. biol. Chem. 266, 19369–19377 (1991).

    CAS  PubMed  Google Scholar 

  20. Czajkowski, C. & Karlin, A. J. biol. Chem. 266, 22603–22612 (1991).

    CAS  PubMed  Google Scholar 

  21. Jackson, M. B. Proc. natn. Acad. Sci. U.S.A. 86, 2219–2203 (1989).

    Article  ADS  Google Scholar 

  22. Sine, S. M., Claudio, T. & Sigworth, F. S. J. gen. Physiol. 96, 395–437 (1990).

    Article  CAS  Google Scholar 

  23. Popot, J.-L. & Changeux, J.-P. Physiol. Rev. 64, 1162–1239 (1984).

    Article  CAS  Google Scholar 

  24. Gorne-Tschelnokow, U. et al. EMBO J. 13, 338–341 (1994).

    Article  CAS  Google Scholar 

  25. Blanton, M. P. & Cohen, J. B. Biochemistry 33, 2859–2872 (1994).

    Article  CAS  Google Scholar 

  26. Stein, P. E. et al. Structure 2, 45–57 (1994).

    Article  CAS  Google Scholar 

  27. Sixma, T. K. et al. Nature 351, 371–377 (1991).

    Article  ADS  CAS  Google Scholar 

  28. Ladenstein, R. et al. J. molec. Biol. 203, 1045–1070 (1988).

    Article  CAS  Google Scholar 

  29. Gerstein, M., Schulz, G. & Chothia, C. J. molec. Biol. 229, 494–501 (1993).

    Article  CAS  Google Scholar 

  30. Akabas, M. H., Stauffer, D. A., Xu, M. & Karlin, A. Science 258, 307–310 (1992).

    Article  ADS  CAS  Google Scholar 

  31. Akabas, M. H., Kaufmann, C., Archdeacon, P. & Karlin, A. Neuron 13, 919–927 (1994).

    Article  CAS  Google Scholar 

  32. Cohen, B. N., Labarca, C., Davidson, N. & Lester, H. A. J. gen. Physiol. 100, 373–400 (1992).

    Article  CAS  Google Scholar 

  33. Dani, J. A. J. Neurosci. 9, 884–892 (1989).

    Article  CAS  Google Scholar 

  34. Giraudat, J. et al. Proc. natn. Acad. Sci. U.S.A. 83, 2719–2723 (1986).

    Article  ADS  CAS  Google Scholar 

  35. Revah, F. et al. Proc. natn. Acad. Sci. U.S.A. 87, 4675–4679 (1990).

    Article  ADS  CAS  Google Scholar 

  36. Hucho, F. L., Oberthur, W. & Lottspeich, F. FEBS Lett. 205, 137–142 (1986).

    Article  CAS  Google Scholar 

  37. White, B. H. & Cohen, J. B. J. biol. Chem. 267, 15770–15783 (1992).

    CAS  PubMed  Google Scholar 

  38. Imoto, K. et al. Nature 335, 645–648 (1988).

    Article  ADS  CAS  Google Scholar 

  39. Charnet, P. et al. Neuron 2, 497–513 (1990).

    Google Scholar 

  40. Imoto, K. et al. FEBS Lett. 289, 193–200 (1991).

    Article  CAS  Google Scholar 

  41. Villarroel, A., Herlitze, S., Koenen, M. & Sakmann, B. Proc. R. Soc. B243, 69–74 (1991).

    Article  ADS  CAS  Google Scholar 

  42. Unwin, N. Neuron 3, 665–676 (1989).

    Article  CAS  Google Scholar 

  43. Lee, Y.-H. et al. Biophys. J. 66, 646–653 (1994).

    Article  ADS  CAS  Google Scholar 

  44. Galzi, J.-L. et al. Nature 359, 500–505 (1992).

    Article  ADS  CAS  Google Scholar 

  45. Eiselé, J.-L. et al. Nature 366, 479–483 (1993).

    Article  ADS  Google Scholar 

  46. Toyoshima, C. & Unwin, N. Ultramicroscopy 25, 279–292 (1988).

    Article  CAS  Google Scholar 

  47. Unwin, P. N. T. & Henderson, R. J. molec. Biol. 94, 425–440 (1975).

    Article  CAS  Google Scholar 

  48. Kubalek, E., Ralston, S., Lindstrom, J. & Unwin, N. J. Cell Biol. 105, 9–18 (1987).

    Article  CAS  Google Scholar 

  49. Sine, S. M. & Steinbach, J. H. Biophys. J. 46, 277–284 (1982).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Unwin, N. Acetylcholine receptor channel imaged in the open state. Nature 373, 37–43 (1995). https://doi.org/10.1038/373037a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/373037a0

  • Springer Nature Limited

This article is cited by

Navigation