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Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides

Nature volume 358, pages 646–653 (1992)Cite this article

Abstract

Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene product with two phosphotyrosyl peptides have been determined by X-ray crystallography at resolutions of 1.5 and 2.0 Å, respectively. A central antiparallel β-sheet in the structure is flanked by two α-helices, with peptide binding mediated by the sheet, intervening loops and one of the helices. The specific recognition of phosphotyrosine involves amino–aromatic interactions between lysine and arginine side chains and the ring system in addition to hydrogen-bonding interactions with the phosphate.

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References

  1. Cantley, L. C. et al. Cell 64, 281–302 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Collett, M. S. & Erickson, R. L. Proc. natn. Acad. Sci. U.S.A. 75, 2021–2024 (1978).

    Article  ADS  CAS  Google Scholar 

  3. Levinson, A. D., Opperman, H. O., Levintow, L., Varmus, H. E. & Bishop, J. M. Cell 15, 561–572 (1978).

    Article  CAS  PubMed  Google Scholar 

  4. Hunter, T. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 77, 1311–1315 (1980).

    Article  ADS  CAS  Google Scholar 

  5. Ullrich, A. & Schlessinger, J. Cell 61, 203–212 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Sadowski, I., Stone, J. C. & Pawson, T. Molec. cell Biol. 6, 4396–4408 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Koch, C. A., Anderson, D., Moran, M. F., Ellis, C. & Pawson, T. Science 252, 668–674 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Margolis, B. et al. Cell 57, 1101–1107 (1989).

    Article  CAS  PubMed  Google Scholar 

  9. Meisenhelder, J., Suh, P.-G., Rhee, S. G. & Hunter, T. Cell 57, 1109 (1989).

    Article  CAS  PubMed  Google Scholar 

  10. McGlade, C. J. et al. Molec. cell Biol. 12, 991–997 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vogel, U. S. et al. Nature 335, 90–93 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Shen, S.-H., Bastein, L., Posner, B. I. & Chrétien, P. Nature 352, 736–739 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Mayer, B. J., Hamaguchi, M. & Hanafusa, H. Nature 332, 272–275 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Matsuda, M., Mayer, B. J., Fukui, Y. & Hanafusa, H. Science 248, 1537–1539 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Mayer, B. J. & Hanafusa, H. J. Virol. 64, 3581–3589 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Anderson, D. et al. Science 250, 979–982 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Mayer, B. J., Jackson, P. K., Van Etten, R. A. & Baltimore, D. Molec. cell Biol. 12, 609–618 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Seidel-Dugan, C., Meyer, B. E., Thomas, S. M. & Brugge, J. M. Molec. cell Biol. 12, 1835–1834 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. O'Brien, M. C., Fukui, Y. & Hanafusa, H. Molec. cell Biol. 10, 2855–2862 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hirai, H. & Varmus, H. E. Molec. cell. Biol. 10, 1307–1318 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Roussel, R. R., Brodeur, S. R., Shalloway, D. & Laudano, A. P. Proc. natn. Acad. Sci. U.S.A. 88, 10696–10700 (1991).

    Article  ADS  CAS  Google Scholar 

  22. DeClue, J. & Martin, G. S. J. Virol. 63, 542–554 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Hirai, H. & Varmus, H. E. Proc. natn. Acad. Sci. U.S.A. 87, 8592–8596 (1990).

    Article  ADS  CAS  Google Scholar 

  24. Overduin, M., Mayer, B., Rios, C. B., Baltimore, D. & Cowburn, D. Proc. natn. Acad. Sci. U.S.A. (in the press).

  25. Overduin, M., Rios, C. B., Mayer, B., Baltimore, D. & Cowburn, D. Cell (in the press).

  26. Margolis, B. L. et al. J. biol. Chem. 264, 10667–10671 (1989).

    CAS  PubMed  Google Scholar 

  27. Kashishian, A., Kazlauskas, A. & Cooper, J. A. EMBO J. 11, 1373–1381 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Birge, R. B., Fajardo, J. E., Mayer, B. J. & Hanafusa, H. J. biol. Chem. 267, 10588–10595 (1992).

    CAS  PubMed  Google Scholar 

  29. Klippel, A., Escobedo, J. A., Fantl, W. J. & Williams, L. T. Molec. cell Biol. 12, 1451–1459 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fantl, W. J. et al. Cell 69, 413–423 (1992).

    Article  CAS  PubMed  Google Scholar 

  31. Hodel, A., Kim, S.-H. & Brünger, A. T. Acta crystallogr. Sect. A. (in the press).

  32. Perutz, M. F., Fermi, G. Abraham, D. J., Poyart, C. & Busaux, E. J. Am. Chem. Soc. 108, 1064–1078 (1986).

    Article  CAS  Google Scholar 

  33. Burley, S. K. & Petsko, G. A. FEBS Lett. 203, 139 (1986).

    Article  CAS  PubMed  Google Scholar 

  34. Wlodawer, A., Walter, J., Huber, R. & Sjölin, L. J. molec. Biol. 180, 301 (1984).

    Article  CAS  PubMed  Google Scholar 

  35. Tüchsen, E. & Woodward, C. H. Biochemistry 26, 1918 (1987).

    Article  PubMed  Google Scholar 

  36. Sussman, J. L. et al. Science 253, 872–879 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  37. Deakyne, C. A. & Moet-Ner, M. J. Am. Chem. Soc. 107, 474 (1985).

    Article  Google Scholar 

  38. Levitt, M. & Perutz, M. F. J. molec. Biol. 201, 751 (1988).

    Article  CAS  PubMed  Google Scholar 

  39. Burley, S. K. & Petsko, G. A. Adv. Prot. Chem. 39, 125–189 (1988).

    CAS  Google Scholar 

  40. Russell, R. B., Breed, J. & Barton, G. J. FEBS Lett. 304, 15–20 (1992).

    Article  CAS  PubMed  Google Scholar 

  41. Bellacosa, A., Testa, J. R., Staal, S. P. & Tsichlis, P. N. Science 254, 274–277 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Bowie, J. U., Lüthy, R. & Eisenberg, D. Science 253, 164–170 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  43. Branden, C. & Tooze, J. Introduction to Protein Structure 1–302 (Garland, New York, 1991).

    Google Scholar 

  44. Quiocho, F. A. & Richards, F. M. Proc. natn. Acad. Sci. U.S.A. 52, 833 (1964).

    Article  ADS  CAS  Google Scholar 

  45. Ringe, D., Petsko, G. A., Yamakura, F., Suzuki, K. & Ohmori, D. Proc. natn. Acad. Sci. U.S.A. 3879–3883 (1983).

  46. Terwilliger, T. C. & Eisenberg, D. Acta crystallogr. A39, 813–817 (1983).

    Article  CAS  Google Scholar 

  47. Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F. & Holmes, K. C. Nature 347, 37–44 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  48. Jones, T. A. & Thirup, S. EMBO J. 5, 819–822 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Acta crystallogr. A47, 110–119 (1991).

    Article  CAS  Google Scholar 

  50. Gregory, R. J., Kammermeyer, K. L., Vincent, W. S. & Wadforth, S. G. Molec. cell Biol. 7, 2119–2127 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nada, S., Okada, M., MacAuley, A., Cooper, J. A. & Nakagawa, H. Nature 351, 69–72 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  52. Takeya, T. & Hanafusa, H. Cell 32, 881–890 (1983).

    Article  CAS  PubMed  Google Scholar 

  53. Czernilofsky, A. P. et al. Nature 310, 736–738 (1983).

    Article  ADS  Google Scholar 

  54. Studier, F. W., Rosenberg, A. H., Dunn, J. J. & Dubendorff, F. W. Meth. Enzym. 185, 60–89 (1990).

    Article  CAS  PubMed  Google Scholar 

  55. Brünger, A. T. X-PLOR (Version 2.2) Manual Yale University, New Haven, CT 06511, 1988).

    Google Scholar 

  56. Weis, W. I., Brünger, A. T., Skehel, J. J. & Wiley, D. C. J. molec. Biol. 212, 737–761 (1990).

    Article  CAS  PubMed  Google Scholar 

  57. Brünger, A. T. Acta crystallogr. Sect. A. 46, 46–57 (1990).

    Article  Google Scholar 

  58. Lee, B. K. & Richards, F. M. J. molec. Biol. 55, 379–400 (1971).

    Article  CAS  PubMed  Google Scholar 

  59. Ul-Haque, M. & Caughlan, C. N. Acta crystallogr. B 26, 1528–1534.

Download references

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Authors and Affiliations

  1. The Rockefeller University, 1230 York Avenue, New York, 10021, USA

    Gabriel Waksman, Dorothea Kominos, Scott C. Robertson, Nalin Pant, David Baltimore, Raymond B. Birge, David Cowburn, Hidesaburo Hanafusa, Bruce J. Mayer, Michael Overduin, Marilyn D. Resh, Carlos B. Rios, Lauren Silverman & John Kuriyan

  2. Howard Hughes Medical Institute, 1230 York Avenue, New York, 10021, USA

    Scott C. Robertson & John Kuriyan

  3. Department of Cell Biology and Genetics, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, 10021, USA

    Marilyn D. Resh & Lauren Silverman

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Waksman, G., Kominos, D., Robertson, S. et al. Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature 358, 646–653 (1992). https://doi.org/10.1038/358646a0

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