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Structural determinants for activation of the α-subunit of a heterotrimeric G protein

Abstract

The 1.8 Å crystal structure of transducin α-GDP, when compared to that of the activated complex with GTP-γS, reveals the nature of the conformational changes that occur on activation of a heterotrimeric G-protein α-subunit. Structural changes initiated by direct contacts with the terminal phosphate of GTP propagate to regions that have been implicated in effector activation. The changes are distinct from those observed in other members of the GTPase superfamily.

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References

  1. Hepler, J. R. & Gilman, A. G. Trends Biochem. Sci. 17, 383–387 (1992).

    Article  CAS  PubMed  Google Scholar 

  2. Simon, M. I., Strathmann, M. P. & Gautam, N. Science 252, 802–808 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Hurley, J. B. J. Bioenerg. Biomembranes 24, 219–226 (1992).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Hargrave, P. A. & Hamm, H. E. in Molecular Pharmacoloy of Cell Regulation Vol. 3 (eds Sibley, D. R. & Houslay, M. D.) 25–67 (Wiley, New York, 1994).

    Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Pai, E. F. et al. Nature 341, 209–214 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Brunger, A. T. et al. Proc. natn. Acad. Sci. U.S.A. 87, 4849–4853 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Tong, L. et al. J. molec. Biol. 217, 503–516 (1991).

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Berchtold, H. et al. Nature 365, 126–132 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Noel, J. P., Hamm, H. E. & Sigler, P. B. Nature 366, 654–663 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Sternweis, P. C. & Gilman, A. C. Proc. natn. Acad. Sci. U.S.A. 79, 4888–4891 (1982).

    Article  ADS  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Faurobert, E. et al. EMBO J. 12, 4191–4198 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miller, R. T. et al. Nature 267, 712–715 (1988).

    Article  ADS  Google Scholar 

  21. Lee, E., Taussig, R. & Gilman, A. G. J. biol. Chem. 267, 1212–1218 (1992).

    CAS  PubMed  Google Scholar 

  22. Clark, K. L., Dignard, D., Thomas, D. Y. & Whiteway, M. Molec. cell. Biol. 13, 1–8 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Whiteway, M. et al. Molec. cell. Biol. (in the press).

  24. Thomas, T. C., Schmidt, C. J. & Neer, E. J. Proc. natn. Acad. Sci. U.S.A. 90, 10295–10298 (1993).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Stryer, L., Hurley, J. B. & Fung, B. K.-K. Meth. Enzym. 96, 617–627 (1983).

    Article  CAS  PubMed  Google Scholar 

  28. Brunger, A. T. Acta. crystallogr. A46, 46–57 (1990).

    Article  Google Scholar 

  29. Brunger, A. T. X-PLOR Version 3.1 Manual (Yale University, 1993).

    Google Scholar 

  30. Jones, T. A. et al. Acta crystallogr. A47, 110–119 (1991).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  33. Robishaw, J. D. et al. Proc. natn. Acad. Sci. U.S.A. 83, 1251–1255 (1986).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  37. Fong, H. K. W., Yoshimoto, K. K., Eversole-Cire, P. & Simon, M. I. Proc. natn. Acad. Sci. U.S.A. 85, 3066–3070 (1988).

    Article  ADS  CAS  Google Scholar 

  38. Nakafuku, M., Itoh, H., Nakamura, S. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 84, 2140–2144 (1987).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  41. Fawzi, A. B. & Northrup, J. K. Biochemistry 29, 3804–3812 (1990).

    Article  CAS  PubMed  Google Scholar 

  42. Higashijima, T. et al. J. biol. Chem. 262, 762–766 (1987).

    CAS  PubMed  Google Scholar 

  43. John, J., Frech, M. & Wittinghofer, A. J. biol. Chem. 263, 11792–11799 (1988).

    CAS  PubMed  Google Scholar 

  44. Kjeldgaard, M. & Nybord, J. J. molec. Biol. 223, 721–742 (1992).

    Article  CAS  PubMed  Google Scholar 

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Lambright, D., Noel, J., Hamm, H. et al. Structural determinants for activation of the α-subunit of a heterotrimeric G protein. Nature 369, 621–628 (1994). https://doi.org/10.1038/369621a0

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