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A structural basis of the interactions between leucine-rich repeats and protein ligands

Nature volume 374, pages 183–186 (1995)Cite this article

Abstract

THE leucine-rich repeat is a recently characterized structural motif1 used in molecular recognition processes as diverse as signal transduction, cell adhesion, cell development, DNA repair and RNA processing2. We present here the crystal structure at 2.5 Å resolution of the complex between ribonuclease A and ribonculease inhibitor, a protein built entirely of leucine-rich repeats. The unusual non-globular structure of ribonuclease inhibitor, its solvent-exposed parallel β-sheet and the conformational flexibility of the structure are used in the interaction; they appear to be the principal reasons for the effectiveness of leucine-rich repeats as protein-binding motifs. The structure can serve as a model for the interactions of other proteins containing leucine-rich repeats with their ligands.

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References

  1. Takahashi, N., Takahashi, Y. & Putnam, F. W. Proc. natn. Acad. Sci. U.S.A. 82, 1906–1910 (1985).

    Article  ADS  CAS  Google Scholar 

  2. Kobe, B. & Deisenhofer, J. Trends biochem. Sci. 19, 415–421 (1994).

    Article  CAS  Google Scholar 

  3. Hofsteenge, J., Kieffer, B., Matthies, R., Hemmings, B. A. & Stone, S. R. Biochemistry 27, 8537–8544 (1988).

    Article  CAS  Google Scholar 

  4. Kobe, B. & Deisenhofer, J. Nature 366, 751–756 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Avey, H. P. et al. Nature 11, 557–562 (1967).

    Article  ADS  Google Scholar 

  6. Kartha, G., Bello, J. & Harker, D. Nature 213, 862–865 (1967).

    Article  ADS  CAS  Google Scholar 

  7. Borkakokti, N. Eur. J. Biochem. 132, 89–94 (1983).

    Article  Google Scholar 

  8. Birdsall, D. L. & McPherson, A. J. biol. Chem. 267, 22230–22236 (1992).

    CAS  PubMed  Google Scholar 

  9. Nachman, J. et al. Biochemistry 29, 928–937 (1990).

    Article  CAS  Google Scholar 

  10. CCP4 Acta crystallogr. D50, 760–763 (1994).

  11. Janin, J. & Chothia, C. J. biol. Chem. 265, 16027–16030 (1990).

    CAS  Google Scholar 

  12. Vicentini, A. M. et al. Biochemistry 29, 8827–8834 (1990).

    Article  CAS  Google Scholar 

  13. Roth, J. S. Biochim. biophys. Acta 21, 34–43 (1956).

    Article  CAS  Google Scholar 

  14. Fominaya, J. M. & Hofsteenge, J. J. biol. Chem. 267, 24655–24660 (1992).

    CAS  Google Scholar 

  15. Wlodawer, A., Svensson, L. A., Sjolin, L. & Gilliland, G. L. Biochemistry 27, 2705–2717 (1988).

    Article  CAS  Google Scholar 

  16. Yoder, M. D., Keen, N. T. & Jurnak, F. Science 260, 1503–1507 (1993).

    Article  ADS  CAS  Google Scholar 

  17. Baumann, U., Wu, S., Flaherty, K. M. & McKay, D. B. EMBO J. 12, 3357–3364 (1993).

    Article  CAS  Google Scholar 

  18. Steinbacher, S. et al. Science 265, 383–386 (1994).

    Article  ADS  CAS  Google Scholar 

  19. Davies, D. R. & Padlan, E. A. Curr. Biol. 2, 254–256 (1992).

    Article  CAS  Google Scholar 

  20. Kobe, B & Deisenhofer, J. J. molec. Biol. 231, 137–140 (1993).

    Article  CAS  Google Scholar 

  21. Kobe, B., Ma, Z. & Diesenhofer, J. J. molec. Biol. 241, 288–291 (1994).

    Article  CAS  Google Scholar 

  22. Otwinowski, Z. Proc. CCP4 Study Weekend (eds Sawyer, L. et al.) 56–62 (SERC, Daresbury Laboratory, Daresbury, UK 1993).

    Google Scholar 

  23. Brünger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).

    Article  ADS  Google Scholar 

  24. Jones, T. A., Bergdoll, M. & Kjeldgaard, M. Crystallography and Modeling Methods in Molecular Design (eds Bugg, C. E. & Ealick, S. E.) 189–195 (Springer, New York, 1990).

    Book  Google Scholar 

  25. Brünger, A. T. Nature 355, 472–475 (1992).

    Article  ADS  Google Scholar 

  26. Luzzati, P. V. Acta crystallogr. 5, 802–810 (1952).

    Article  Google Scholar 

  27. Read, R. J. Acta crystallogr. A42, 140–149 (1986).

    Article  Google Scholar 

  28. Carson, M. J. molec. Graphics 5, 103–106 (1987).

    Article  CAS  Google Scholar 

  29. Nicholls, A. & Honig, B. J. comp. Chem. 12, 435–445 (1991).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

Download references

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Author notes

  1. Bostjan Kobe

    Present address: St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia

Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75235-9050, USA

    Bostjan Kobe & Johann Deisenhofer

  2. on leave from Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, Jamova 39, 61111, Ljubljana, Slovenia

    Bostjan Kobe

Authors
  1. Bostjan Kobe
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  2. Johann Deisenhofer
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Kobe, B., Deisenhofer, J. A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature 374, 183–186 (1995). https://doi.org/10.1038/374183a0

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