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.

  • Letter
  • Published:

Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form

Abstract

THE Ran proteins constitute a distinct branch of the superfamily of Ras-related GTP-binding proteins1 which function as molecular switches cycling between GTP-bound 'on' and GDP-bound 'off states2. Ran is located predominantly in the nucleus of eukaryotic cells3 and is involved in the nuclear import of proteins4,5 as well as in control of DNA synthesis and of cell-cycle progression6–8. We report here the crystal structure at 2.3 Å resolution of human Ran (Mr 24K) complexed with GDP and Mg2+. This structure reveals a similarity with the Ras core (G-domain) but with significant variations in regions involved in GDP and Mg2+ coordination (switch I and switch II regions in Ras)9,10, suggesting that there could be major conformational changes upon GTP binding. In addition to the G-domain, an extended chain and an α-helix were identified at the carboxy terminus. The amino-terminal (amino-acid residues 1MAAQGEP7) stretch and the acidic tail (211DEDDDL216) appear to be flexible in the crystal structure.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Valencia, A., Chardin, P., Wittinghofer, A. & Sander, C. Biochemistry 30, 4637–4648 (1991).

    Article  CAS  Google Scholar 

  2. Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 348, 125–131 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Bischoff, F. R. & Ponstingl, H. Prac. natn. Acad. Sci. U.S.A. 88, 10830–10834 (1991).

    Article  ADS  CAS  Google Scholar 

  4. Moore, M. S. & Blobel, G. Nature 365, 661–663 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Melchior, F., Paschal, B., Evans, J. & Gerace, L. J. Cell Biol. 123, 1649–1659 (1993).

    Article  CAS  Google Scholar 

  6. Kornbluth, S., Dasso, M. & Newport, J. J. Cell Biol. 125, 705–719 (1994).

    Article  CAS  Google Scholar 

  7. Ren, M., Coutavas, E., D'Eustachio, P. & Rush, M. G. Molec. cell. Biol. 14, 4216–4224 (1994).

    Article  CAS  Google Scholar 

  8. Clarke, P. R., Klebe, C., Wittinghofer, A. & Karsenti, E. J. Cell Sci. (in the press).

  9. Milburn, M. V. et al. Science 247, 939–945 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Wittinghofer, A. & Pai, E. Trends biochem. Sci. 16, 383–387 (1991).

    Article  Google Scholar 

  11. Pai, E. F. et al. Nature 341, 209–214 (1989).

    Article  ADS  CAS  Google Scholar 

  12. Jurnak, F. Science 230, 32–36 (1985).

    Article  ADS  CAS  Google Scholar 

  13. LaCour, T. F. M., Nyborg, J., Thirup, S. & Clark, B. F. C. EMBO J. 4, 2385–2388 (1985).

    Article  CAS  Google Scholar 

  14. Berchtold, H. et al. Nature 365, 126–132 (1993).

    Article  ADS  CAS  Google Scholar 

  15. Noel, J. P., Hamm, H. E. & Sigler, P. B. Nature 366, 654–663 (1993).

    Article  ADS  CAS  Google Scholar 

  16. Coleman, D. E. et al. Science 265, 1405–1412 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Czworkoski, J., Wang, J., Steitz, T. A. & Moore, P. B. EMBO J. 13, 3661–3668 (1994).

    Article  Google Scholar 

  18. Ævarsson, A. et al. EMBO J. 13, 3669–3677 (1994).

    Article  Google Scholar 

  19. Klebe, C., Nishimoto, T. & Wittinghofer, F. Biochemistry 32, 11923–11928 (1993).

    Article  CAS  Google Scholar 

  20. Ohtsubo, M., Okazaki, H. & Nishimoto, T. J. Cell Biol. 109, 1389–1397 (1989).

    Article  CAS  Google Scholar 

  21. Bischoff, F. R., Klebe, C., Kretschmer, J., Wittinghofer, A. & Ponstingl, H. Proc. natn. Acad. Sci. U.S.A. 91, 2587–2591 (1994).

    Article  ADS  CAS  Google Scholar 

  22. Coutavas, E., Ren, M., Oppenheim, J. D., D'Eustachio, P. & Rush, M. G. Nature 366, 585–587 (1993).

    Article  ADS  CAS  Google Scholar 

  23. Klebe, C., Bischoff, F. R., Ponstingl, H. & Wittinghofer, A. Biochemistry 34, 639–647 (1995).

    Article  CAS  Google Scholar 

  24. Lounsbury, K. M., Beddow, A. L. & Macara, I. G. J. biol. Chem. 269, 11285–11290 (1994).

    CAS  PubMed  Google Scholar 

  25. Kabsch, W. J. appl. Crystallogr. 26, 795–800 (1993).

    Article  CAS  Google Scholar 

  26. Tong, L., de Vos, A. M., Milburn, M. V. & Kim, S.-H. J. molec. Biol. 217, 503–516 (1991).

    Article  CAS  Google Scholar 

  27. Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjelgaard, M. Acta crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  28. Brünger, A. T. X-PLOR (Version 3.1) (Yale Univ., New Haven, 1993).

    Google Scholar 

  29. Kabsch, W. & Sander, C. Biopolymers 22, 2577–2637 (1983).

    Article  CAS  Google Scholar 

  30. Kraulis, P. J. J. appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scheffzek, K., Klebe, C., Fritz-Wolf, K. et al. Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form. Nature 374, 378–381 (1995). https://doi.org/10.1038/374378a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/374378a0

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