Abstract
The X-ray crystal structure of the complex between the Ras-related protein RaplA in the GTP-analogue (GppNHp) form and the Ras-binding domain (RBD) of the Ras effector molecule c-Raf1, a Ser/Thr-specific protein kinase, has been solved to a resolution of 2.2 Å. It shows that RBD has the ubiquitin superfold and that the structure of RaplA is very similar to that of Ras. The interaction between the two proteins is mediated by an apparent central antiparallel β-sheet formed by strands B1–B2 from RBD and strands β2–β3 from RaplA. Complex formation is mediated by main-chain and side-chain interactions of the so-called effector residues in the switch I region of RaplA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Daum, G., Eisenmann-Tappe, I., Fries, H.-W., Troppmair, J. & Rapp, U. R. Trends biochem. Sci. 19, 474–480 (1994).
Burgering, B. M. T. & Bos, J. L. Trends biochem. Sci. 20, 18–22 (1995).
Koide, H., Satoh, T., Nakafuku, M. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 90, 8683–8686 (1993).
Moodie, S. A., Willumsen, B. M., Weber, M. J. & Wolfman, A. Science 260, 1658–1661 (1993).
van Aelst, L., Barr, M., Marcus, S., Polverino, A. & Wigler, M. Proc. natn. Acad. Sci. U.S.A. 90, 6213–6217 (1993).
Vojtek, A. B., Hollenberg, S. M. & Cooper, J. A. Cell 74, 205–214 (1993).
Zhang, X. F. et al. Nature 364, 308–313 (1993).
Warne, P. H., Rodriguez Viciana, P. & Downward, J. Nature 364, 352–355 (1993).
Leevers, S. J., Paterson, H. F. & Marshall, C. J. Nature 369, 411–414 (1994).
Stokoe, D., Macdonald, S. G., Cadwallader, K., Symons, M. & Hancock, J. F. Science 264, 1463–1467 (1994).
Emerson, S. D. et al. Biochemistry 33, 7745–7752 (1994).
Chuang, E. et al. Molec. cell. biol. 14, 5318–5325 (1994).
Herrmann, C., Martin, G. A. & Wittinghofer, A. J. biol. Chem. 270, 2901–2905 (1995).
Pizon, V., Chardin, P., Lerosey, I., Olofsson, B. & Tavitian, A. Oncogene 3, 201–204 (1988).
Bokoch, G. in GTPases in Biology I, Vol. 108/1 (eds Dickey, B. F. & Birnbaumer, L.) 377–393 (Springer, Berlin and Heidelberg, 1993).
Frech, M. et al. Science 249, 169–171 (1990).
Hata, Y. et al. J. biol. Chem. 265, 7104–7107 (1990).
Hofer, F., Fields, S., Schneider, C. & Martin, G. S. Proc. natn. Acad. Sci. U.S.A. 91, 11089–11093 (1994).
Kikuchi, A., Demo, S. D., Ye, Z.-H., Chen, Y.-W. & Williams, L. T. Molec. cell. Biol. 14, 7483–7491 (1994).
Spaargaren, M. & Bishoff, J. R. Proc. natn. Acad. Sci. U.S.A. 91, 12609–12613 (1994).
Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. & Noda, M. Cell 56, 77–84 (1989).
Hariharen, I. K., Carthew, R. W. & Rubin, G. M. Cell 67, 717–722 (1991).
Cook, S., Rubinfeld, B., Albert, I. & McCormick, F. EMB0 J. 12, 3475–3485 (1993).
Pai, E. F. et al. EMBO J. 9, 2351–2359 (1990).
Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjelgaard, M. Acta crystallogr. A47, 110–119 (1991).
Brunger, T. A. XPLOR version 3.1, Yale Univ. (1993).
Read, R. J. Acta crystallogr. A42, 140–149 (1986).
Brunger, T. A. Nature 355, 472–475 (1992).
Milburn, M. V. et al. Science 247, 939–945 (1990).
Amor, J. C., Harrison, D. H., Kahn, R. A. & Ringe, D. Nature 372, 704–708 (1994).
Scheffzek, K., Klebe, C., Fritz-Wolf, K., Kabsch, W. & Wittinghofer, A. Nature 374, 378–381 (1995).
Marshall, M. S. Trends biochem. Sci. 18, 250–254 (1993).
Polakis, P. & McCormick, F. J. biol. Chem. 268, 9157–9160 (1993).
Schlichting, I. et al. Nature 345, 309–315 (1990).
Vijay-Kumar, S., Bugg, C. E. & Cook, W. J. J. molec. Biol. 194, 531–544 (1987).
Orengo, C. A., Jones, D. T. & Thornton, J. M. Nature 372, 631–634 (1994).
Connolly, M. L. J. appl. Crystallogr. 16, 548–558 (1983).
Janin, J. & Chothia, C. J. biol. Chem. 265, 16027–16030 (1990).
Lawrence, M. C. & Colman, P. M. J. molec. Biol. 234, 946–950 (1993).
Calés, C., Hancock, J. F., Marshall, C. J. & Hall, A. Nature 332, 548–551 (1988).
Fabian, J. R., Vojtek, A. B., Cooper, A. & Morrison, D. K. Proc. natn. Acad. Sci. U.S.A. 91, 5982–5986 (1994).
Barnard, D. et al. Oncogene 10, 1283–1290 (1995).
Lu, X., Melnick, M. B., Hsu, J.-C. & Perrimon, N. EMBO J. 13, 2592–2599 (1994).
White, M. et al. Cell 80, 1–20 (1995).
Gibbs, J. B. & Oliff, A. Cell 79, 193–198 (1994).
Kabsch, W. J. appl. Crystallogr. 26, 795–800 (1993).
Navaza, J. Acta crystallogr. A50, 157–163 (1994).
Kabsch, W. & Sander, C. Biopolymers 22, 2577–2637 (1983).
Kraulis, P. J. appl. Crystallogr. 24, 946–950 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nassar, N., Horn, G., Herrmann, C. et al. The 2.2 Å crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with RaplA and a GTP analogue. Nature 375, 554–560 (1995). https://doi.org/10.1038/375554a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/375554a0
This article is cited by
-
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
Signal Transduction and Targeted Therapy (2023)
-
Inhibition mechanism of MRTX1133 on KRASG12D: a molecular dynamics simulation and Markov state model study
Journal of Computer-Aided Molecular Design (2023)
-
Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding
Nature Communications (2022)
-
Elevated expression of RIT1 hyperactivates RAS/MAPK signal and sensitizes hepatocellular carcinoma to combined treatment with sorafenib and AKT inhibitor
Oncogene (2022)
-
Afadin couples RAS GTPases to the polarity rheostat Scribble
Nature Communications (2022)
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.
