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Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting

Nature volume 381, pages 248–251 (1996)Cite this article

Abstract

THE signal-recognition particle (SRP) is important for the targeting of many secretory and membrane proteins to the endoplasmic reticulum (ER). Targeting is regulated by three GTPases, the 54K subunit of SRP (SRP54), and the α- and β-subunits of the SRP receptor1. When a signal sequence emerges from the ribosome, SRP interacts with it and targets the resulting complex to the ER membrane by binding to the SRP receptor. Subsequently, SRP releases the signal sequence into the translocation channel2,3. Here we use a complex of a ribosome with a nascent peptide chain, the SRP and its receptor, to investigate GTP binding to SRP54, and GTP hydrolysis. Our findings indicate that a ribosomal component promotes GTP binding to the SRP54 subunit of SRP. GTP-bound SRP54 is essential for high-affinity interaction between SRP and its receptor in the ER membrane. This interaction induces the release of the signal sequence from SRP, the insertion of the nascent polypeptide chain into the translocation channel, and GTP hydrolysis. The contribution of the ribosome had previously escaped detection because only synthetic signal peptides were used in the analysis4.

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References

  1. Walter, P. & Johnson, A. E. A. Rev. Cell Biol. 10, 87–119 (1994).

    Article  CAS  Google Scholar 

  2. Rapoport, T. A. Science 258, 931–936 (1992).

    Article  ADS  CAS  Google Scholar 

  3. Lütcke, H. Eur. J. Biochem. 228, 531–550 (1995).

    Article  Google Scholar 

  4. Miller, J. D., Wilhelm, H., Gierasch, L., Gilmore, R. & Walter, P. Nature 366, 351–354 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Nath, J. P., Eagle, G. R. & Himes, R. H. Biochemistry 24, 1555–1560 (1985).

    Article  CAS  Google Scholar 

  6. Grand, R. J. & Owen, D. Biochem. J. 279, 609–631 (1991).

    Article  CAS  Google Scholar 

  7. Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 349, 117–127 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Rapiejko, P. J. & Gilmore, R. Molec. Biol. Cell 5, 887–897 (1994).

    Article  CAS  Google Scholar 

  9. Hwang, Y.-W. & Miller, D. L. J. biol. Chem. 262, 13081–13085 (1987).

    CAS  PubMed  Google Scholar 

  10. Görlich, D., Prehn, S., Hartmann, E., Kalies, K.-U. & Rapoport, T. A. Cell 71, 489–503 (1992).

    Google Scholar 

  11. Görlich, D., Hartmann, E., Prehn, S. & Rapoport, T. A. Nature 357, 47–52 (1992).

    Article  ADS  Google Scholar 

  12. Hauser, S., Bacher, G., Dobberstein, B. & Lütcke, H. EMBO J. 14, 5485–5493 (1995).

    Article  CAS  Google Scholar 

  13. Jungnickel, B. & Rapoport, T. A. Cell 82, 261–270 (1995).

    Article  CAS  Google Scholar 

  14. Lauring, B., Sakai, H., Kreibich, G. & Wiedmann, M. Proc. natn. Acad. Sci. U.S.A. 92, 5411–5415 (1995).

    Article  ADS  CAS  Google Scholar 

  15. Rapiejko, P. J. & Gilmore, R. J. Cell Biol. 117, 493–503 (1992).

    Article  CAS  Google Scholar 

  16. Connolly, T. & Gilmore, R. J. Cell Biol. 103, 2253–2261 (1986).

    Article  CAS  Google Scholar 

  17. Connolly, T. & Gilmore, R. J. Cell Biol. 123, 799–807 (1993).

    Article  CAS  Google Scholar 

  18. Connolly, T., Rapiejko, P. J. & Gilmore, R. Science 252, 1171–1173 (1991).

    Article  ADS  CAS  Google Scholar 

  19. Connolly, T. & Gilmore, R., Cell 57, 599–610 (1989).

    Article  CAS  Google Scholar 

  20. Görlich, D. & Rapoport, T. A. Cell 75, 615–630 (1993).

    Article  Google Scholar 

  21. Luirink, J. et al. Nature 359, 741–743 (1992).

    Article  ADS  CAS  Google Scholar 

  22. Stueber, D., Ibrahimi, I., Cutler, D., Dobberstein, B. & Bujard, H. EMBO J. 3, 3143–3148 (1984).

    Article  CAS  Google Scholar 

  23. Walter, P., Ibrahimi, I. & Blobel, G. J. Cell Biol. 91, 545–550 (1981).

    Article  CAS  Google Scholar 

  24. Nakamaye, K. L. & Eckstein, F. Nucleic Acids Res. 14, 9679–9698 (1986).

    Article  CAS  Google Scholar 

  25. Wiedmann, M., Kurzchalia, T. V., Bielka, H. & Rapoport, T. A. J. Cell Biol. 104, 201–208 (1987).

    Article  CAS  Google Scholar 

  26. High, S., Görlich, D., Wiedmann, M., Rapoport, T. A. & Dobberstein, B. J. Cell Biol. 113, 35–44 (1991).

    Article  CAS  Google Scholar 

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Author notes

  1. Berit Jungnickel and Tom A. Rapoport: Harvard Medical School, Department of Cell Biology, 25 Shattuck Street, Boston, Massachusetts 02115, USA

Authors and Affiliations

  1. Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120, Heidelberg, Germany

    Gerald Bacher, Henrich Lütcke, Berit Jungnickel, Tom A. Rapoport & Bernhard Dobberstein

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  1. Gerald Bacher
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  2. Henrich Lütcke
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  3. Berit Jungnickel
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  4. Tom A. Rapoport
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  5. Bernhard Dobberstein
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Bacher, G., Lütcke, H., Jungnickel, B. et al. Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting. Nature 381, 248–251 (1996). https://doi.org/10.1038/381248a0

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