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
Freedman, R. B. Cell 57, 1069–1072 (1989).
Braakman, I., Helenius, J. & Helenius, A. EMBO J. (in the press).
Braakman, I., Hoover-Litty, H., Wagner, K. R. & Helenius, A. J. Cell Biol. 114, 401–411 (1990).
Creighton, T. E. Prog. Biophys. Molec. Biol. 33, 231–297 (1978).
Clarke, B. L. & Weigel, P. H. J. biol. Chem. 260, 128–133 (1985).
Podbilewicz, B. & Mellman, I. EMBO J. 9, 3477–3487 (1990).
Hurtley, S. M., Bole, D. G., Hoover-Litty, H., Helenius, A. & Copeland, C. S. J. Cell Biol. 108, 2117–2126 (1989).
Copeland, C. S., Doms, R. W., Bolzau, E. M., Webster, R. G. & Helenius, A. J. Cell Biol. 103, 1179–1191 (1986).
Haas, I. G. & Wabl, M. Nature 306, 387–389 (1983).
Bole, D. G., Hendershot, L. M. & Kearney, J. F. J. Cell Biol. 102, 1558–1566 (1986).
Dorner, A. J., Bole, D. G. & Kaufman, R. J. J. Cell Biol. 105, 2665–2674 (1987).
Kassenbrock, C. K., Garcia, P. D., Walter, P. & Kelly, R. B. Nature 333, 90–93 (1988).
Kozutsumi, Y., Segal, M., Normington, K., Gething, M.-J. & Sambrook, J. Nature 332, 462–464 (1988).
Bochkareva, E. S., Lissin, N. M. & Girshovich, A. S. Nature 336, 254–257 (1988).
Laminet, A. A., Ziegelhoffer, T., Georgopoulos, C. & Plückthun, A. EMBO J. 9, 2315–2319 (1990).
Martin, J. et al. Nature 352, 36–42 (1991).
Ellis, R. J. & Van der Vies, S. M. A. Rev. Biochem. 60, 321–347 (1991).
Doms, R. W., Keller, D. S., Helenius, A. & Balch, W. E. J. Cell Biol. 105, 1957–1969 (1987).
Lévy, F., Gabathuler, R., Larsson, R. & Kvist, S. Cell 67, 265–274 (1991).
Clairmont, C., Demaio, A. and Hirschberg, C. J. Cell Biol. 115, 255a (1991).
Kassenbrock, C. K. & Kelly, R. B. EMBO J. 8, 1461–1467 (1989).
Munro, S. & Pelham, H. R. B. Cell 46, 291–300 (1986).
Gething, M.-J. & Sambrook, J. Semin. Cell Biol. 1, 65–72 (1990).
Rothman, J. E. Cell 59, 591–601 (1989).
Pelham, H. R. B. Cell 46, 959–961 (1986).
Flynn, G. C., Chappel, T. G. & Rothman, J. E. Science 245, 385–390 (1989).
Dorner, A. J., Wasley, L. C. & Kaufman, R. J. Proc. natn. Acad. Sci. U.S.A. 87, 7429–7432 (1990).
Gething, M.-J., McCammon, K. & Sambrook, J. Cell 46, 939–950 (1986).
Gottlieb, C., Baenziger, J. & Kornfeld, S. J. biol. Chem. 250, 3303–3309 (1975).
Balch, W. E., Elliott, M. M. & Keller, D. S. J. Cell Biol. 261, 14681–14689 (1986).
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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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DOI: https://doi.org/10.1038/356260a0
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