Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Structure and ligand recognition of the phosphotyrosine binding domain of Shc

Abstract

The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of She complexed to a phosphopeptide reveals an alternative means of recognizing tryosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel β-strand with a β-sheet of the protein, interacts with a hydrophobic pocket through the (pY–5) residue, and adopts a β-turn. The PTB domain is structurally similar to pleckstrin homology domains (a β-sandwich capped by an α-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Giorgetti, S., Pelicci, P. G., Pelicci, G. & Van Obberghen, E. Eur. J. Biochem. 223, 195–202 (1994).

    Article  CAS  Google Scholar 

  2. Pelicci, G. et al. Cell 70, 93–104 (1992).

    Article  CAS  Google Scholar 

  3. Rozakis-Adcock, M. et al. Nature 360, 689–692 (1992).

    Article  ADS  CAS  Google Scholar 

  4. Stephens, R. M. et al. Neuron 12, 691–705 (1994).

    Article  CAS  Google Scholar 

  5. Obermeier, A. et al. EMBO J. 13, 1585–1590 (1994).

    Article  CAS  Google Scholar 

  6. Ravichandran, K. S. & Burakoff, S. J. J. biol. Chem. 269, 1599–1602 (1993).

    Google Scholar 

  7. Burns, L. A., Karnitz, L. M., Sutor, S. L. & Abraham, R. T. J. biol. Chem. 268, 17659–17661 (1993).

    CAS  PubMed  Google Scholar 

  8. Sato, N., Sakamaki, K., Terada, N., Arai, K. & Miyajima, A. EMBO J. 12, 4181–4189 (1993).

    Article  CAS  Google Scholar 

  9. Ravichandran, K. S. et al. Science 262, 902–905 (1993).

    Article  ADS  CAS  Google Scholar 

  10. Saxton, T., van Oostveen, I., Bowtell, D., Aebersold, R. & Gold, M. J. Immun. 153, 623–636 (1994).

    CAS  PubMed  Google Scholar 

  11. Egan, S. E. Nature 363, 45–51 (1993).

    Article  ADS  CAS  Google Scholar 

  12. van Biesen, T. et al. Nature 376, 781–784 (1995).

    Article  ADS  CAS  Google Scholar 

  13. Lev, S. et al. Nature 376, 737–745 (1995).

    Article  ADS  CAS  Google Scholar 

  14. Kavanaugh, W. M. & Williams, L. T. Science 266, 1862–1865 (1994).

    Article  ADS  CAS  Google Scholar 

  15. Blaikie, P. et al. J. biol. Chem. 269, 32031–32034 (1994).

    CAS  PubMed  Google Scholar 

  16. Gustafson, T. A., He, W., Craparo, A., Schaub, C. D. & O'Neill, T. J. Molec. cell. Biol. 15, 2500–2508 (1995).

    Article  CAS  Google Scholar 

  17. Songyang, Z. et al. Molec. cell. Biol. 14, 2777–2785 (1994).

    Article  CAS  Google Scholar 

  18. Songyang, Z., Margolis, B., Chaudhur, M., Shoelson, S. E. & Cantley, L. C. J. biol. Chem. 270, 14863–14866 (1995).

    Article  CAS  Google Scholar 

  19. Trüb, T. et al. J. biol. Chem. 270, 18205–18208 (1995).

    Article  Google Scholar 

  20. Kavanaugh, W. M., Turck, C. W. & Williams, L. T. Science 268, 1177–1179 (1995).

    Article  ADS  CAS  Google Scholar 

  21. van der Geer, P. et al. Curr. Biol. 5, 404–412 (1995).

    Article  CAS  Google Scholar 

  22. Zhou, M.-M. et al. J. biol. Chem. 270, 31119–31123 (1995).

    Article  CAS  Google Scholar 

  23. Dikic, I. et al. J. biol. Chem. 270, 15125–15129 (1985).

    Article  Google Scholar 

  24. O'Neill, T. J., Craparo, A. & Gustafson, T. A. Molec. cell. Biol. 14, 6433–6442 (1994).

    Article  CAS  Google Scholar 

  25. Bork, P. & Margolis, B. Cell 80, 693–694 (1995).

    Article  CAS  Google Scholar 

  26. Sun, X. J. et al. Nature 377, 173–177 (1995).

    Article  ADS  CAS  Google Scholar 

  27. Yamazaki, T., Lee, W., Arrowsmith, C. H., Muhandiram, D. R. & Kay, L. E. J. Am. chem. Soc. 116, 11655–11666 (1994).

    Article  CAS  Google Scholar 

  28. Nilges, M., Clore, G. M. & Gronenborn, A. M. FEBS Lett. 229, 317–324 (1988).

    Article  CAS  Google Scholar 

  29. Kuszewski, J., Nilges, M. & Brünger, A. T. J. biomolec. NMR 2, 33–56 (1992).

    Article  CAS  Google Scholar 

  30. Wilmot, C. M. & Tnornton, J. M. J. molec. Biol. 203, 221–232 (1988).

    Article  CAS  Google Scholar 

  31. Bansal, A. & Gierasch, L. M. Cell 67, 1195–1201 (1991).

    Article  CAS  Google Scholar 

  32. Eck, M. J., Shoelson, S. E., & Harrison, S. C. Nature 362, 87–91 (1993).

    Article  ADS  CAS  Google Scholar 

  33. Waksman, G., Shoelson, S. E., Pant, N., Cowburn, D. & Kuriyan, J. Cell 72, 779–790 (1993).

    Article  CAS  Google Scholar 

  34. Zhou, M.-M. et al. Proc. natn. Acad. Sci. U.S.A. 92, 7784–7788 (1995).

    Article  ADS  CAS  Google Scholar 

  35. Flower, D. R. FEBS Lett. 333, 99–102 (1993).

    Article  CAS  Google Scholar 

  36. Saraste, M. & Hyvönen, M. Curr. Opin. struct. Biol. 5, 403–408 (1995).

    Article  CAS  Google Scholar 

  37. Musacchio, A. et al. Trends biochem. Sci. 18, 343–348 (1993).

    Article  CAS  Google Scholar 

  38. Touhara, K. et al. J. biol. Chem. 269, 10217–10220 (1994).

    CAS  Google Scholar 

  39. Harlan, J. E., Hajduk, P. J., Yoon, H. S. & Fesik, S. W. Nature 371, 168–170 (1994).

    Article  ADS  CAS  Google Scholar 

  40. Silvius, J. R. & I'Heureax, F. Biochemistry 33, 3014–3022 (1994).

    Article  CAS  Google Scholar 

  41. Peitzsch, R. M. & Mclaughlin, S. Biochemistry 32, 10436–10443 (1993).

    Article  CAS  Google Scholar 

  42. Brooks, B. R. et al. J. comput. Chem. 4, 187–217 (1983).

    Article  CAS  Google Scholar 

  43. Carson, M. J. molec. Graph. 5, 103–106 (1987).

    Article  CAS  Google Scholar 

  44. Clore, G. M. & Gronenborn, A. M. Meth. Enzym. 239, 349–363 (1994).

    Article  CAS  Google Scholar 

  45. Brünger, A. T. X-PLOR Manual, version 3.1 (Yale Univ. Press, Cambridge, MA, 1992).

    Google Scholar 

  46. Kuboniwa, H., Grzesiek, S., Delaglio, F. & Bax, A. J. biomolec. NMR 4, 871–878 (1994).

    Article  CAS  Google Scholar 

  47. Yoon, H. S. et al. Nature 369, 672–675 (1994).

    Article  ADS  CAS  Google Scholar 

  48. Hope, M. J., Bally, M. B., Webb, G. & Cullis, P. R. Biochim. biophys. Acta 812, 55–65 (1985).

    Article  CAS  Google Scholar 

  49. Tortorella, D. & London, E. Analyt. Biochem. 217, 176–180 (1994).

    Article  CAS  Google Scholar 

  50. Rebecchi, M., Peterson, A. & McLaughlin, S. Biochemistry 31, 12742–12747 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, MM., Ravichandran, K., Olejniczak, E. et al. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature 378, 584–592 (1995). https://doi.org/10.1038/378584a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/378584a0

This article is cited by

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing