Abstract
The structure of a heterotrimeric G protein reveals the mechanism of the nucleotide-dependent engagement of the α and βγ subunits that regulates their interaction with receptor and effector molecules. The interaction involves two distinct interfaces and dramatically alters the conformation of the αbut not of theβγ subunits. The location of the known sites for posttranslational modification and receptor coupling suggest a plausible orientation with respect to the membrane surface and an activated heptahelical receptor.
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
Conklin, B. R. & Bourne, H. R. Cell 73, 631–641 (1993).
Neer, E. J. Cell 80, 249–257 (1995).
Simon, M. I., Strathmann, M. P. & Gautam, N. Science 252, 802–808 (1991).
Hepler, J. R. & Gilman, A. G. Trends biochem. Sci. 17, 383–387 (1992).
Crespo, P., Xu, N., Simonds, W. F. & Gutkind, J. S. Nature 369, 418–420 (1994).
Faure, M., Voyno-Yasenetskaya, A. & Bourne, H. R. J. biol. Chem. 269, 7851–7854 (1994).
Hurley, J. B. J. Bioenerg. Biomem. 24, 219–226 (1992).
Pfister, C. et al. Cell Sig. 5, 235–241 (1993).
Lambridght, D. G., Noel, J. P., Hamm, H. E. & Sigler, P. B. Nature 369, 621–628 (1994).
Noel, J. P., Hamm, H. E. & Sigler, P. B. Nature 366, 654–663 (1993).
Sondek, J, S., Lambright, D. G., Noel, J. P., Hamm, H. E. & Sigler, P. B. Nature 372, 276–279 (1994).
Coleman, D. E. et al. Science 265, 1405–1412 (1994).
Skiba, N. et al. J. biol. Chem. 271, 413–424 (1996).
Mixon, M. B. et al. Science 270, 954 (1995). (Initial?)
Neer, E. J., Schmidt, C. J., Nambudripad, R. & Smith, T. F. Nature 371, 297–300 (1994).
Fung, B. K. & Nash, C. R. J. biol. Chem. 258, 10503–10510 (1983).
Mazzoni, M. R. & Hamm, H. E. Biochemistry 28, 9873–9880 (1989).
Mazzoni, M. R., Malinski, J. A. & Hamm, H. E. J. biol. Chem. 266, 14072–14081 (1991).
Graf, R., Mattera, R., Codina, J., Estes, M. K. & Birnbaumer, L. J. biol. Chem. 267, 24307–24314 (1992).
Denker, B. M., Neer, E. J. & Schmidt, C. J. biol. Chem. 267, 6272–6277 (1992).
Slepak, V. Z., Wilkie, T. M. & Simon, M. I. J. biol. Chem 268, 1414–1423 (1993).
Miller, R. T. et al. Nature 267, 712–715 (1988).
Lee, E., Taussig, R. & Gilman, A. G. J. biol. Chem. 267, 1212–1218 (1992).
Garcia-Higuera, I., Thomas, T. C., Yi, F. & Neer, E. J. J. biol. Chem. 271, 528 (1996).
Whiteway, M., Clark, K. L., Leberer, E., Dignard, D. & Thomas, D. Y. Molec. cell. Biol. 14, 3223–3229 (1994).
Sondek, J., Bohm, A., Lambright, D. G., Hamm, H. E. & Sigler, P. B. Nature 379, 369–374 (1996).
Higashijima, T., Ferguson, K. M., Sternweis, P. C., Murray, D. S. & Gilman, A. G. J. biol. Chem. 262, 762–766 (1987).
Fukada, Y. et al. Nature 346, 658–660 (1990).
Lai, R. K., Dolores, P.-S., Canada, F. J. & Rando, R. R. Proc. natn. Acad. Sci. U.S.A. 87, 7673–7677 (1990).
Mumby, S. M., Casey, P. J., Gilman, A. G., Gutowski, S. & Sternweis, P. C. Proc. natn. Acad. Sci. U.S.A. 87, 5873–5877 (1990).
Yamane, H. K. et al. Proc. natn. Acad. Sci. U.S.A. 87, 5868–5872 (1990).
Maltese, W. A. & Robishaw, J. D. J. biol. Chem. 265, 18071–18074 (1990).
Buss, J. E., Mumbry, S. M., Casey, P. J., Gilman, A. G. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 84, 7493–7497 (1987).
Kokame, K., Fukada, Y., Yoshizawa, T., Takao, T. & Shimonishi, Y. Nature 359, 749–752 (1992).
Neubert, T. A., Johnson, R. S., Hurley, J. B. & Walsh, K. A. J. biol. Chem. 267, 18274–18277 (1992).
Linder, M. E. et al. Proc. natn. Acad. Sci. U.S.A. 90, 3675–3679 (1993).
Wedegaertner, P. B. & Bourne, H. R. Cell 77, 1063–1070 (1994).
Linder, M. E. et al. J. biol. Chem. 266, 4654–4659 (1991).
Iniguez-Lluhi, J. A., Simon, M. I., Robishaw, J. D. & Gilman, A. G. J. biol. Chem. 267, 23409–23417 (1992).
Bigay, J., Faurobert, E., Franco, M. & Chabre, M. Biochemistry 33, 14081–14090 (1994).
West, R. E., Moss, J., Vaughan, M., Liu, T. & Liu, T. Y. J. biol. Chem. 260, 14428–14430.
Sullivan, K. A. et al. Nature 330, 758–760 (1987).
Hirsch, J. P., Dietzel, C. & Kurjan, J. Genes Dev. 5, 467–474 (1991).
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).
Conklin, B. R., Farfel, Z., Lustig, K. D., Julius, D. & Bourne, H. R. Nature 363, 274–276 (1993).
Hamm, H. E. et al. Science 241, 832–835 (1988).
Dratz, E. A. et al. Nature 363, 276–281 (1993).
Phillips, W. J. & Cerione, R. A. J. biol. Chem. 267, 17032–17039 (1992).
Stryer, L., Hurley, J. B. & Fung, B. K.-K. Meth. Enzym. 96, 617–627 (1983).
Kabsch, W. J. appl. Crystallogr. 21, 67–71 (1988).
Brunger, A. T. Acta crystallogr. A46, 46–57 (1990).
Brunger, A. T. X-PLOR version 3.1 Manual (Yale University, 1993).
Jones, T. A. et al. Acta crystallogr. A47, 110–119 (1991).
Grishin, A. V., Weiner, J. L. & Blumer, K. Molec. cell. Biol. 14, 4571–4578 (1994).
Leberer, E. et al. EMBO J. 11, 4805–4813 (1992).
Nicholls, A., Sharp, K. A. & Honig, B. Proteins 11, 281–296 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lambright, D., Sondek, J., Bohm, A. et al. The 2.0 Å crystal structure of a heterotrimeric G protein. Nature 379, 311–319 (1996). https://doi.org/10.1038/379311a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/379311a0
This article is cited by
-
Beyond the G protein α subunit: investigating the functional impact of other components of the Gαi3 heterotrimers
Cell Communication and Signaling (2023)
-
Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones
Pflügers Archiv - European Journal of Physiology (2021)
-
Rational design and implementation of a chemically inducible heterotrimerization system
Nature Methods (2020)
-
Structural underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor
Nature Communications (2019)
-
G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling
Cellular and Molecular Life Sciences (2019)
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.