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:

Structural basis for the interaction of Ras with RaIGDS

Nature Structural Biology volume 5, pages 422–426 (1998)Cite this article

Abstract

The Ras protein signals to a number of distinct pathways by interacting with diverse downstream effectors. Among the effectors of Ras are the Raf kinase and RalGDS, a guanine nucleotide dissociation stimulator specific for Ral. Despite the absence of significant sequence similarities, both effectors bind directly to Ras, but with different specificities. We report here the 2.1 Å crystal structure of the complex between Ras and the Ras-interacting domain (RID) of RalGDS. This structure reveals that the β-sheet of the RID joins the switch I region of Ras to form an extended β-sheet with a topology similar to that found in the Rap–Raf complex. However, the side chain interactions at the joining junctions of the two interacting systems and the relative orientation of the two binding domains are distinctly different. Furthermore, in the case of the Ras–RID complex a second RID molecule also interacts with a different part of the Ras molecule, the switch II region. These findings account for the cross-talk between the Ras and Ral pathways and the specificity with which Ras distinguishes the two effectors.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Hall, A. Curr. Opin. Cell Biol. 5, 265–268 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Vojtek, A.B., Hollenberg, S.M. & Cooper, J.A. Cell 74, 205–214 (1993).

    Article  CAS  Google Scholar 

  4. Nassar, N. et al. Nature 375, 554–560 (1995).

    Article  CAS  Google Scholar 

  5. Brtva, T.R. et al. J. Biol. Chem. 270, 9809–9812 (1995).

    Article  CAS  Google Scholar 

  6. Hu, Q., Klippel, A., Muslin, A.J., Fantl, W.J. & Williams, L.T. Science 268, 100–102 (1995).

    Article  CAS  Google Scholar 

  7. Hofer, F., Fields, S., Schneider, C. & Martin, G.S. Proc. Watl. Acad. Sci. USA 91, 11089–11093 (1994).

    Article  CAS  Google Scholar 

  8. Spaargaren, M. & Bischoff, J.R. Proc. Natl. Acad. Sci. USA 91, 12609–12613 (1994).

    Article  CAS  Google Scholar 

  9. Kikuchi, A., Demo, S.D., Ye, Z.H., Chen, Y.W. & Williams, L.T. Mol. Cell. Biol. 14, 7483–7491 (1994).

    Article  CAS  Google Scholar 

  10. Ponting, C.P. & Benjamin, D.R. Trends Biochem. Sci. 21, 422–425 (1996).

    Article  CAS  Google Scholar 

  11. Herrmann, C., Horn, G., Spaargaren, M. & Wittenghofer, A. J. Biol. Chem. 271, 6794–6800 (1996).

    Article  CAS  Google Scholar 

  12. Huang, L., Weng, X., Hofer, F., Martin, G.S. & Kim, S.-H. Nature Struct. Biol. 4, 609–615 (1997).

    Article  CAS  Google Scholar 

  13. Geyer, M., Herrmann, C., Wohlgemuth, S., Wittinghofer, A. & Kalbitzer, H.R. Nature Struct. Biol. 4, 694–699 (1997).

    Article  CAS  Google Scholar 

  14. White, M.A. et al. Cell 80, 533–541 (1995).

    Article  CAS  Google Scholar 

  15. White, M.A., Vale, T., Camonis, J.H., Schaefer, E. & Wigler, M.H. J. Biol. Chem. 271, 16439–16442 (1996).

    Article  CAS  Google Scholar 

  16. Khosravi-Far, R. et al. Mol. Cell. Biol. 16, 3923–3933 (1996).

    Article  CAS  Google Scholar 

  17. Joneson, T., White, M., Wigler, M.H. & Bar-Sagi, D. Science 271, 810–812 (1996).

    Article  CAS  Google Scholar 

  18. Okazaki, M. et al. Oncogene 14, 515–521 (1997).

    Article  CAS  Google Scholar 

  19. Katz, M.E. & McCormick, F. Curr. Opin. Genet. Dev. 7, 75–79 (1997).

    Article  CAS  Google Scholar 

  20. Feig, L.A., Urano, T. & Cantor, S. Trends Biochem. Sci 21, 438–441 (1996).

    Article  CAS  Google Scholar 

  21. Urano, T., Emkey, R. & Feig, L.A. EMBO. J. 15, 810–816 (1996).

    Article  CAS  Google Scholar 

  22. Hwang, M.C., Sung, Y.J. & Hwang, Y.W. J. Biol. Chem. 271, 8196–8202 (1996).

    Article  CAS  Google Scholar 

  23. Nassar, N. et al. Nature Struct. Biol. 3, 723–729 (1996).

    Article  CAS  Google Scholar 

  24. Miura, K. et al. Jap. J. Cancer Res. 77, 45–51 (1986).

    CAS  Google Scholar 

  25. Pai, E.F. et al. EMBO J. 9, 2351–2359 (1990).

    Article  CAS  Google Scholar 

  26. Huang, L., Lancarik, J., Kim, S.-H., Hofer, F. & Martin, G.S. Acta Crystallogr. D 52, 1033–1035 (1996).

    Article  CAS  Google Scholar 

  27. Brunger, A.T. X-PLOR, version 3.85 (Yale University, New Haven, Connecticut; 1996).

    Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Kraulis, P.J. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  30. Merritt, E.A. & Murphy, M.E.P. Acta Crystallogr D. 50, 869–873 (1994).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  32. Nicholls, A., Sharp, K.A. & Honig, B. Proteins Struct Funct Genet. 11, 281–296 (1991).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and E. O. Lawrence Berkeley National Laboratory, University of California, Berkeley, California, 94720, USA

    Lan Huang & Sung-Hou Kim

  2. Department of Molecular and Cell Biology, University of California, Berkeley, California, 94720, USA

    Franz Hofer & G. Steven Martin

Authors
  1. Lan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franz Hofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Steven Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sung-Hou Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung-Hou Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, L., Hofer, F., Martin, G. et al. Structural basis for the interaction of Ras with RaIGDS. Nat Struct Mol Biol 5, 422–426 (1998). https://doi.org/10.1038/nsb0698-422

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsb0698-422

This article is cited by

Search

Advanced 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