Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The 2.2 Å crystal structure of transducin-α complexed with GTPγS

Abstract

The 2.2 Å crystal structure of activated rod transducin, G-GTPγS, shows the bound GTPγS molecule occluded deep in a cleft between a domain structurally homologous to small GTPases and a helical domain unique to heterotrimeric G proteins. The structure, when combined with biochemical and genetic studies, suggests: how an activated receptor might open this cleft to allow nucleotide exchange; a mechanism for GTP-induced changes in effector and receptor binding surfaces; and a mechanism for GTPase activity not evident from previous data.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Conklin, B. R. & Bourne, H. R. Cell 73, 631–641 (1993).

    Article  CAS  Google Scholar 

  2. Blumer, K. J. & Thorner, J. A. Rev. Physiol. 53, 37–57 (1991).

    Article  CAS  Google Scholar 

  3. Tang, W. J., Krupinski, J. & Gilman, A. G. J. biol. Chem. 266, 8595–8603 (1991).

    CAS  PubMed  Google Scholar 

  4. Berstein, G. et al. Cell 70, 411–418 (1992).

    Article  CAS  Google Scholar 

  5. Arshavsky, V. Y. & Bownds, M. D. Nature 357, 416–418 (1992).

    Article  ADS  Google Scholar 

  6. Stryer, L. & Bourne, H. R. A. Rev. Cell Biol. 2, 391–419 (1986).

    Article  CAS  Google Scholar 

  7. Pfister, C. et al. Cell Sig. 5, 235–241 (1993).

    Article  CAS  Google Scholar 

  8. Liebman, P. A., Parker, K. R. & Dratz, E. A. A. Rev. Physiol. 49, 765–791 (1987).

    Article  CAS  Google Scholar 

  9. Mazzoni, M. R., Malinski, J. A. & Hamm, H. E. J. biol. Chem. 266, 14072–14081 (1991).

    CAS  PubMed  Google Scholar 

  10. Jones, T. A. J. appl. Crystallogr. 11, 268–276 (1978).

    Article  CAS  Google Scholar 

  11. Brunger, A. T. XPLOR Version 3.1 Manual Yale Univ. (1993).

    Google Scholar 

  12. Pai, E. F. et al. EMBO J. 9, 2351–2359 (1990).

    Article  CAS  Google Scholar 

  13. Berchtold, H. Nature 365, 126–132 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Jurnak, F. Science 230, 32–36 (1985).

    Article  ADS  CAS  Google Scholar 

  15. La Cour, T. F. M., Nyborg, J., Thirup, S. & Clark, B. F. C. EMBO J. 4, 191–212 (1985).

    Article  Google Scholar 

  16. Saraste, M., Sibbald, P. R. & Wittinghofer, A. Trends biochem. Sci. 15, 430–434 (1990).

    Article  Google Scholar 

  17. Milburn, M. V. et al. Science 247, 939–945 (1990).

    Article  ADS  CAS  Google Scholar 

  18. Van Dop, C., Tsubokawa, M., Bourne, H. R. & Ramachandran, J. J. biol. Chem. 259, 696–698 (1984).

    CAS  Google Scholar 

  19. Hamm, H. E. et al. Science 241, 832–835 (1988).

    Article  ADS  CAS  Google Scholar 

  20. Dratz, E. A. et al. Nature 363, 276–281 (1993).

    Article  ADS  CAS  Google Scholar 

  21. Conklin, B. R., Farfel, Z., Lustig, K. D., Julius, D. & Bourne, H. R. Nature 363, 274–276 (1993).

    Article  ADS  CAS  Google Scholar 

  22. Simonds, W. F., Goldsmith, P. K., Codina, J., Unson, C. G. & Spiegel, A. M. Proc. natn. Acad. Sci. U.S.A. 86, 7809–7813 (1989).

    Article  ADS  CAS  Google Scholar 

  23. Gilman, A. G. A. Rev. Biochem. 56, 615–649 (1987).

    Article  CAS  Google Scholar 

  24. Van Dop, C. et al. J. biol. Chem. 259, 23–26 (1984).

    CAS  PubMed  Google Scholar 

  25. Fung, B. K.-K. & Nash, C. R. J. biol. Chem. 258, 10503–10510 (1983).

    CAS  PubMed  Google Scholar 

  26. Mazzoni, M. R. & Hamm, H. E. J. Prot. Chem. 12, 215–221 (1993).

    Article  CAS  Google Scholar 

  27. Higashijima, T. et al. J. biol. Chem. 262, 752–756 (1987).

    CAS  PubMed  Google Scholar 

  28. Kaziro, Y. Biochem. biophys. Acta 505, 95–127 (1978).

    CAS  PubMed  Google Scholar 

  29. Downward, J., Riehl, R., Wu, L. & Weinberg, R. A. Proc. natn. Acad. Sci. U.S.A. 87, 5998–6002 (1990).

    Article  ADS  CAS  Google Scholar 

  30. Rarick, H. M., Artemyev, N. O. & Hamm, H. E. Science 256, 1031–1033 (1992).

    Article  ADS  CAS  Google Scholar 

  31. Berlot, C. H. & Bourne, H. R. Cell 68, 911–922 (1992).

    Article  CAS  Google Scholar 

  32. Miller, R. T., Masters, S. B., Sullivan, K. A., Beiderman, B. & Bourne, H. R. Nature 334, 712–715 (1988).

    Article  ADS  CAS  Google Scholar 

  33. Artemyev, N. O. et al. J. biol. Chem. 268, 23611–23615 (1993).

    CAS  PubMed  Google Scholar 

  34. Gupta, S. K. et al. J. molec. cell. Biol. 12, 190–197 (1992).

    Article  CAS  Google Scholar 

  35. Landis, C. A. et al. Nature 340, 692–696 (1989).

    Article  ADS  CAS  Google Scholar 

  36. Gibbs, J. B., Sigal, I. S. & Scolnick, E. M. Trends biochem. Sci. 10, 350–353 (1985).

    Article  CAS  Google Scholar 

  37. Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 348, 125–132 (1990).

    Article  ADS  CAS  Google Scholar 

  38. Kabsch, W. J. appl. Crystallogr. 21, 67–71 (1988).

    Article  CAS  Google Scholar 

  39. Kabsch, W. J. appl. Crystallogr. 21, 916–924 (1988).

    Article  CAS  Google Scholar 

  40. Otwinowski, Z. ML-PHARE CCP4 Proc. 80–88 (Daresbury Laboratory, Warrington, UK, 1991).

  41. Zhang, K. Y. Acta crystallogr. D49, 213–222 (1993).

    CAS  Google Scholar 

  42. Brunger, A. T. Nature 355, 472–475 (1992).

    Article  ADS  CAS  Google Scholar 

  43. Carson, M. J. appl. Crystallogr. 24, 958–961 (1991).

    Article  Google Scholar 

  44. Robishaw, J. D., Russell, D. W., Harris, B. A., Smigel, M. D. & Gilman, A. G. Proc. natn. Acad. Sci. U.S.A. 83, 1251–1255 (1986).

    Article  ADS  CAS  Google Scholar 

  45. Nukada, T. et al. FEBS Lett. 197, 305–308 (1986).

    Article  CAS  Google Scholar 

  46. Van Meurs, K. P. et al. Proc. natn. Acad. Sci. U.S.A. 84, 3107–3111 (1987).

    Article  ADS  CAS  Google Scholar 

  47. Strathmann, M. & Simon, M. I. Proc. natn. Acad. Sci. U.S.A. 87, 9113–9117 (1990).

    Article  ADS  CAS  Google Scholar 

  48. Casey, P. J., Fong, H. K. W., Simon, M. I. & Gilman, A. G. J. biol. Chem. 265, 2383–2390 (1990).

    CAS  PubMed  Google Scholar 

  49. Yatsunami, K. & Khorana, H. G. Proc. natn. Acad. Sci. U.S.A. 82, 4316–4320 (1985).

    Article  ADS  CAS  Google Scholar 

  50. Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. Nature 302, 33–37 (1983).

    Article  ADS  CAS  Google Scholar 

  51. Laursen, R. A., L'ltalien, J. J., Nagarkatti, S. & Miller, D. L. J. biol. Chem. 256, 8102–8109 (1981).

    CAS  PubMed  Google Scholar 

  52. Steitz, T. A. & Story, R. M. Proc. The Robert A. Welch Foundation Conference on Chemical Research XXXVI Regulation of Proteins by Ligands 173–186 (Houston, 1992).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Noel, J., Hamm, H. & Sigler, P. The 2.2 Å crystal structure of transducin-α complexed with GTPγS. Nature 366, 654–663 (1993). https://doi.org/10.1038/366654a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/366654a0

This article is cited by

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing