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Role of ATP and disulphide bonds during protein folding in the endoplasmic reticulum

Nature volume 356, pages 260–262 (1992)Cite this article

Abstract

BEING topologically equivalent to the extracellular space, the lumen of the endoplasmic reticulum (ER) provides a unique folding environment for newly synthesized proteins. Unlike other compartments in the cell where folding occurs, the ER is oxidizing and therefore can promote the formation of disulphide bonds1. The reducing agent dithiothreitol, when added to living cells, inhibits disulphide formation with profound effects on folding2. Taking advantage of this effect, we demonstrate here that folding of influenza haemagglutinin is energy dependent. Metabolic energy is required to support the correct folding and disulphide bond formation in this well characterized viral glycoprotein, to rescue misfolded proteins from disulphide-linked aggregates, and to maintain the oxidized protein in its folded and oligomerization-competent state.

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References

  1. Freedman, R. B. Cell 57, 1069–1072 (1989).

    Article  CAS  Google Scholar 

  2. Braakman, I., Helenius, J. & Helenius, A. EMBO J. (in the press).

  3. Braakman, I., Hoover-Litty, H., Wagner, K. R. & Helenius, A. J. Cell Biol. 114, 401–411 (1990).

    Article  Google Scholar 

  4. Creighton, T. E. Prog. Biophys. Molec. Biol. 33, 231–297 (1978).

    Article  CAS  Google Scholar 

  5. Clarke, B. L. & Weigel, P. H. J. biol. Chem. 260, 128–133 (1985).

    CAS  PubMed  Google Scholar 

  6. Podbilewicz, B. & Mellman, I. EMBO J. 9, 3477–3487 (1990).

    Article  CAS  Google Scholar 

  7. Hurtley, S. M., Bole, D. G., Hoover-Litty, H., Helenius, A. & Copeland, C. S. J. Cell Biol. 108, 2117–2126 (1989).

    Article  CAS  Google Scholar 

  8. Copeland, C. S., Doms, R. W., Bolzau, E. M., Webster, R. G. & Helenius, A. J. Cell Biol. 103, 1179–1191 (1986).

    Article  CAS  Google Scholar 

  9. Haas, I. G. & Wabl, M. Nature 306, 387–389 (1983).

    Article  ADS  CAS  Google Scholar 

  10. Bole, D. G., Hendershot, L. M. & Kearney, J. F. J. Cell Biol. 102, 1558–1566 (1986).

    Article  CAS  Google Scholar 

  11. Dorner, A. J., Bole, D. G. & Kaufman, R. J. J. Cell Biol. 105, 2665–2674 (1987).

    Article  CAS  Google Scholar 

  12. Kassenbrock, C. K., Garcia, P. D., Walter, P. & Kelly, R. B. Nature 333, 90–93 (1988).

    Article  ADS  CAS  Google Scholar 

  13. Kozutsumi, Y., Segal, M., Normington, K., Gething, M.-J. & Sambrook, J. Nature 332, 462–464 (1988).

    Article  ADS  CAS  Google Scholar 

  14. Bochkareva, E. S., Lissin, N. M. & Girshovich, A. S. Nature 336, 254–257 (1988).

    Article  ADS  CAS  Google Scholar 

  15. Laminet, A. A., Ziegelhoffer, T., Georgopoulos, C. & Plückthun, A. EMBO J. 9, 2315–2319 (1990).

    Article  CAS  Google Scholar 

  16. Martin, J. et al. Nature 352, 36–42 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Ellis, R. J. & Van der Vies, S. M. A. Rev. Biochem. 60, 321–347 (1991).

    Article  CAS  Google Scholar 

  18. Doms, R. W., Keller, D. S., Helenius, A. & Balch, W. E. J. Cell Biol. 105, 1957–1969 (1987).

    Article  CAS  Google Scholar 

  19. Lévy, F., Gabathuler, R., Larsson, R. & Kvist, S. Cell 67, 265–274 (1991).

    Article  Google Scholar 

  20. Clairmont, C., Demaio, A. and Hirschberg, C. J. Cell Biol. 115, 255a (1991).

    Google Scholar 

  21. Kassenbrock, C. K. & Kelly, R. B. EMBO J. 8, 1461–1467 (1989).

    Article  CAS  Google Scholar 

  22. Munro, S. & Pelham, H. R. B. Cell 46, 291–300 (1986).

    Article  CAS  Google Scholar 

  23. Gething, M.-J. & Sambrook, J. Semin. Cell Biol. 1, 65–72 (1990).

    CAS  PubMed  Google Scholar 

  24. Rothman, J. E. Cell 59, 591–601 (1989).

    Article  CAS  Google Scholar 

  25. Pelham, H. R. B. Cell 46, 959–961 (1986).

    Article  CAS  Google Scholar 

  26. Flynn, G. C., Chappel, T. G. & Rothman, J. E. Science 245, 385–390 (1989).

    Article  ADS  CAS  Google Scholar 

  27. Dorner, A. J., Wasley, L. C. & Kaufman, R. J. Proc. natn. Acad. Sci. U.S.A. 87, 7429–7432 (1990).

    Article  ADS  CAS  Google Scholar 

  28. Gething, M.-J., McCammon, K. & Sambrook, J. Cell 46, 939–950 (1986).

    Article  CAS  Google Scholar 

  29. Gottlieb, C., Baenziger, J. & Kornfeld, S. J. biol. Chem. 250, 3303–3309 (1975).

    CAS  Google Scholar 

  30. Balch, W. E., Elliott, M. M. & Keller, D. S. J. Cell Biol. 261, 14681–14689 (1986).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06510-8002, USA

    Ineke Braakman, Jonne Helenius & Ari Helenius

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  1. Ineke Braakman
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  2. Jonne Helenius
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  3. Ari Helenius
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Braakman, I., Helenius, J. & Helenius, A. Role of ATP and disulphide bonds during protein folding in the endoplasmic reticulum. Nature 356, 260–262 (1992). https://doi.org/10.1038/356260a0

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