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Three-Dimensional Structure of ras p21 Proteins

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The Guanine — Nucleotide Binding Proteins

Abstract

ras genes (review in Barbacid, 1987) have been found in a large number of eukaryotic organisms, from Saccharomyces and Drosophila to chicken, rat, and man. Moreover, ras gene products of various species show a very high degree of homology: even between proteins from yeast and man there is approximately 54% identity between corresponding amino acids, and ras proteins from chicken and man differ only in three amino acids. Such evolutionary conservation implies an important cellular function for these proteins, and they have indeed been implicated in playing a crucial role in cell proliferation and terminal differentiation. Based on these observations and on biochemical similarities with G-proteins, it is thought that ras proteins participate as signal transducers at the beginning of the cascade of reactions leading to various essential cellular processes.

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References

  • Adari, H., Lowy, D. R., Willumsen, B. M., Der, C. J., and McCormick, F., 1988, Guanosine triphosphate activating protein (GAP) interacts with the p21 ras effector binding domain, Science, 240:518.

    Article  PubMed  CAS  Google Scholar 

  • Barbacid, M., 1987, ras Genes, Ann. Rev. Biochem., 56:779.

    Article  PubMed  CAS  Google Scholar 

  • Cales, C., Hancock, J. F., Marshall, C. J., and Hall, A., 1988, The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product, Nature, 332:548.

    Article  PubMed  CAS  Google Scholar 

  • Dever, T. E., Glynias, M. J., and Merrick, W. C., 1987, GTP-binding domain: three consensus sequence elements with distinct spacing, Proc. Natl. Acad. Sci. USA, 84:1814.

    Article  PubMed  CAS  Google Scholar 

  • De Vos, A. M., Tong, L., Milburn, M. V., Matias, P. M., Jancarik, J., Noguchi, S., Nishimura, S., Miura, K., Ohtsuka, E., and Kim, S.-H., 1988, Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21, Science, 239:888.

    Article  PubMed  Google Scholar 

  • Eccleston, J. F. and Webb, M. R., 1982, Characterization of the GTPase reaction of elongation factor Tu, J. Biol. Chem., 257:5046.

    PubMed  CAS  Google Scholar 

  • Gibbs, J. B., Sigal, I. S., Poe, M., and Scolnick, E. M., 1984, Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules, Proc. Natl. Acad. Sci. USA, 81:5704.

    Article  PubMed  CAS  Google Scholar 

  • Jancarik, J., De Vos, A. M., Kim, S.-H., Miura, K., Ohtsuka, E., Noguchi, S., and Nishimura, S., 1988, Crystallization of human c-H-ras oncogene products, J. Mol. Biol., 200:205.

    Article  PubMed  CAS  Google Scholar 

  • Jurnak, F., 1985, Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins, Science, 230:32.

    Article  PubMed  CAS  Google Scholar 

  • Kim, S.-H., De Vos, A. M., Tong, L., Milburn, M. V., Matias, P. M., Jancarik, J., Ohtsuka, E., and Nishimura, S., 1988, ras oncogene proteins: three-dimensional structures, functional implications, and a model for signal transduction, Cold Spring Harbor Symp., in press.

    Google Scholar 

  • Lacal, J. C., Anderson, P. S., and Aaronson, S. A., 1986, Deletion mutants of Harvey ras p21 protein reveal the absolute requirement of at least two distant regions for GTP-binding and transforming activities, EMBO J., 5:679.

    PubMed  CAS  Google Scholar 

  • McGrath, J. P., Capon, D. J., Goeddel, D. V., and Levinson, A. D., 1984, Comparative properties of normal and activated human ras p21 protein, Nature, 310:644.

    Article  PubMed  CAS  Google Scholar 

  • La Cour, T. F. M., Nyborg, J., Thirup, S., and Clark, B. F. C., 1985, Structural details of the binding of guanosine diphosphate to elongation factor Tu from E. coli as studied by X-ray crystallography, EMBO J., 4:2385.

    PubMed  Google Scholar 

  • McCormick, F., Clark, B. F. C., La Cour, T. F. M., Kjeldgaard, M., Norskov-Lauritsen, L., and Nyborg, J., 1985, A model for the tertiary structure of p21, the product of the ras oncogene, Science, 230:78.

    Article  PubMed  CAS  Google Scholar 

  • Miura, K., Inoue, Y., Nakamori, H., Iwai, S., Ohtsuka, E., Ikehora, M., Noguchi, S., and Nishimura, S., 1986, Synthesis and expression of a synthetic gene for the activated human c-Ha-ras protein, Jpn. J. Canc. Res. (Gann), 77:45.

    CAS  Google Scholar 

  • Nishimura, S. and Sekiya, T., 1987, Human cancer and cellular oncogenes, Biochem. J., 243:313.

    PubMed  CAS  Google Scholar 

  • Rao, S. T. and Rossmann, M. G., 1973, Comparison of super-secondary structures in proteins, J. Mol. Biol., 76:241.

    Article  PubMed  CAS  Google Scholar 

  • Reddy, E. P., Reynolds, R. K., Santos, E., and Barbacid, M., 1982, A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene, Nature, 300:149.

    Article  PubMed  CAS  Google Scholar 

  • Scolnick, E. M., Papageorge, A. G., and Shih, T. Y., 1979, Guanine nucleotide-binding activity and an assay for src protein of rat-derived murine sarcoma viruses, Proc. Natl. Acad. Sci. USA, 76:5355.

    Article  PubMed  CAS  Google Scholar 

  • Seeburg, P. H., Colby, W. W., Capon, D. J., Goeddel, D. V., and Levinson, A. D., 1984, Biological properties of human c-Ha-ras1 genes mutated at codon 12, Nature, 312:71.

    Article  PubMed  CAS  Google Scholar 

  • Shih, T. Y., Stokes, P. E., Smythers, G. W., Dhar, D., and Oroszlan, S., 1982, Characterization of the phosphorylation sites and the surrounding amino acid sequences of the p21 transforming proteins coded for by the Harvey and Kirsten strains of murine sarcoma viruses, J. Biol. Chem., 257:11767.

    PubMed  CAS  Google Scholar 

  • Sigal, I. S., Gibbs, J. B., D’Alonzo, J. S., and Scolnick, E. M., 1986, Identification of effector residues and a neutralizing epitope of Ha-ras-encoded p21, Proc. Natl. Acad. Sci. USA, 83:4725.

    Article  PubMed  CAS  Google Scholar 

  • Sweet, R. W., Yokoyama, S., Kamata, T., Feramisco, J. R., Rosenberg, M., and Gross, M., 1984, The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity, Nature, 311:273.

    Article  PubMed  CAS  Google Scholar 

  • Tabin, C. J., Bradley, S. M., Bargmann, C. I., Weinberg, R. A., Papageorge, A. G., Scolnick, E. M., Dhar, R., Lowy, D. R., and Chang, E. H., 1982, Mechanism of activation of a human oncogene, Nature, 300:143.

    Article  PubMed  CAS  Google Scholar 

  • Taparowski, E., Suard, Y., Fasano, O., Shimizu, K., Goldfarb, M., and Wigier, M., 1982, Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change, Nature, 300:762.

    Article  Google Scholar 

  • Tronrud, D. E., Ten Eyck, L. F., and Matthews, B. W., 1987, An efficient general-purpose least-squares program for macromolecular structures, Acta Cryst., A43:489.

    CAS  Google Scholar 

  • Webb, M. R. and Eccleston, J. F., 1981, The stereochemical course of the ribosome-dependent GTPase reaction of elongation factor G from Escherichia coli, J. Biol. Chem., 256:7734.

    CAS  Google Scholar 

  • Willumsen, B. M., Christensen, A., Hubbert, N. L., Papageorge, A., and Lowy, D. R., 1984, The p21 ras C-terminus is required for transformation and membrane association, Nature, 310:583.

    Article  PubMed  CAS  Google Scholar 

  • Willumsen, B. M., Papageorge, A., Hubbert, N. L., Bekesi, E., Kung, H.-F., and Lowy, D. R., 1985, Transforming p21 ras protein: flexibility in the major variable region linking the catalytic and membrane-anchoring domains, EMBO J., 4:2893.

    PubMed  CAS  Google Scholar 

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de Vos, A.M., Tong, L., Milburn, M.V., Matias, P.M., Kim, SH. (1989). Three-Dimensional Structure of ras p21 Proteins. In: Bosch, L., Kraal, B., Parmeggiani, A. (eds) The Guanine — Nucleotide Binding Proteins. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2037-2_3

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  • DOI: https://doi.org/10.1007/978-1-4757-2037-2_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-2039-6

  • Online ISBN: 978-1-4757-2037-2

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