Abstract
One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene1–4. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 Å resolution and compare it with the structure of the normal c-Ha-ras protein5. One of the major differences is that the loop of the transforming ras protein that binds the β-phosphate of the guanine nucleotide is enlarged. Such a change in the "catalytic site' conformation could explain the reduced GTPase activity of the mutant6–8, which keeps the protein in the GTP bound 'signal on9 state for a prolonged period of time, ultimately causing cell transformation.
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
Barbacid, M. A. Rev. Biochem. 56, 779–828 (1987).
Tabin, C. J. et al. Nature 300, 143–149 (1982).
Reddy, E. P., Reynolds, R. K., Santos, E. & Barbacid, M. Nature 300, 149–152 (1982).
Taparowsky, E. et al. Nature 300, 762–765 (1982).
De Vos, A. M. et al. Science 239, 888–893 (1988).
Gibbs, J. B., Sigal, I. S., Poe, M. & Scolnick, E. M. Proc. natn. Acad. Sci. U.S.A. 81, 5704–5708 (1984).
McGrath, J. P., Capon, D. J., Goeddel, D. V. & Levinson, A. D. Nature 310, 644–649 (1984).
Sweet, R. W. et al. Nature 311, 273–275 (1984).
Miura, K. et al. Jap. J. Cancer Res. 77, 45–51 (1986).
Jancarik, J. et al. J. molec. Biol. 200, 205–207 (1988).
Shimizu, K. et al. Nature 304, 497–500 (1983).
Willumsen, B. M. et al. EMBO J. 4, 2893–2896 (1985).
Rossmann, M. G. J. appl. Crystallogr. 13, 225–238 (1979).
Steigemann, W. thesis, Technische Univ. München (1974).
Tronrud, D. E., Ten Eyck, L. F. & Matthews, B. W. Acta crystallogr. A43, 489–501 (1987).
Sigal, I. S., Gibbs, J. B., D'Alonzo, J. S. & Scolnick, E. M. Proc. natn. Acad. Sci. U.S.A. 83, 4725–4729 (1986).
Stone, J. C., Vass, W. C., Willumsen, B. M. & Lowy, D. R. Molec. cell. Biol. 8, 3565–3569 (1988).
Calés, C., Hancock, J. F., Marshall, C. J. & Hall, A. Nature 332, 548–551 (1988).
Adari, M., Lowy, D. R., Willumsen, B. M., Der, C. J. & McCormick, F. Science 240, 518–521 (1988).
Eccleston, T. F. & Webb, M. R. J. biol. Chem. 257, 5046–5049 (1982).
Shin, T. Y., Stokes, P. E., Smythers, G. W., Dhar, D. & Oroszlan, S. J. biol. Chem. 257, 11767–11786 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tong, L., de Vos, A., Milburn, M. et al. Structural differences between a ras oncogene protein and the normal protein. Nature 337, 90–93 (1989). https://doi.org/10.1038/337090a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/337090a0
This article is cited by
-
Ras oncogenes: split personalities
Nature Reviews Molecular Cell Biology (2008)
-
Transformation of vascular endothelial cells by a point mutation in the Tie2 gene from human intramuscular haemangioma
Oncogene (2004)
-
An unusual H-Ras mutant isolated from a human multiple myeloma line leads to transformation and factor-independent cell growth
Oncogene (2003)
-
Oncogenic insertional mutations in the P-loop of Ras are overactive in MAP kinase signaling
Oncogene (2000)
-
Missense mutation in the gene encoding the α subunit of rod transducin in the Nougaret form of congenital stationary night blindness
Nature Genetics (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.
