Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin

Abstract

The formation of disulphide bonds is essential to the structure and function of proteins. These bonds rapidly form either co-translationally or immediately post-translationally in the lumen of the endoplasmic reticulum1,2. Native disulphide pairing for such proteins has been achieved in vitro; however, the rates of reassembly are slow and the conditions non-physiological3,4. To account for these observations, Anfinsen et al. proposed that a ‘disulphide interchange protein’ was the in vivo catalyst of disulphide bond rearrangement5. Other groups discovered an activity with similar characteristics that catalysed the reductive cleavage of insulin and may be associated with insulin degradation6,7, although this result has been disputed8. The enzyme involved, protein disulphide isomerase (PDI; EC 5.3.4.1), may be the in vivo catalyst of disulphide bond formation9. Here we describe the sequence of cloned rat liver PDI complementary DNA which predicts a protein with two distinct regions homologous with Escherichia coli thioredoxin, a known cofactor in oxidation–reduction reactions10. Each of these regions contains the presumed active site sequence Trp-Cys-Gly-His-Cys-Lys, suggesting that PDI, similar in action to thioredoxin, catalyses disulphide bond interchange via an internal disulphide–sulphydryl interchange. The cDNA predicts a signal peptide consistent with the view that PDI is a luminal endoplasmic reticulum protein. PDI messenger RNA, although ubiquitous, is more highly concentrated in secretory cells.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bergman, L. W. & Kuehl, W. M. J. biol. Chem. 254, 5690–5694 (1979).

    CAS  PubMed  Google Scholar 

  2. Peters, T. & Davidson, L. K. J. biol. Chem. 257, 8847–8853 (1982).

    CAS  PubMed  Google Scholar 

  3. Freedman, R. B. & Hillson, D. A. in The Enzymology of Post-Translational Modifications of Proteins (eds Freeman, R. B. & Hawkins, H. C.) 167–212 (Academic, New York, 1980).

    Google Scholar 

  4. Anfinsen, C. B. & Scheraga, H. A. Adv. Protein Chem. 29, 205–300 (1975).

    Article  CAS  PubMed  Google Scholar 

  5. Goldberger, R. F., Epstein, C. J. & Anfinsen, C. B. J. biol. Chem. 238, 628–635 (1963).

    CAS  PubMed  Google Scholar 

  6. Tomizawa, H. J. biol. Chem. 237, 428–431 (1962).

    CAS  PubMed  Google Scholar 

  7. Katzen, H. M. & Stetten, D. Diabetes 11, 271–280 (1962).

    CAS  PubMed  Google Scholar 

  8. Duckworth, W. C. & Kitabchi, A. E. Endocrine Rev. 2, 778–782 (1983).

    Google Scholar 

  9. Freedman, R. B. Trends biochem. Sci. 9, (1984).

  10. Holmgren, A. Eur. J. Biochem. 6, 475–484 (1968).

    Article  CAS  PubMed  Google Scholar 

  11. Freedman, R. B., Brockway, B. E. & Lambert, N. Biochem. Soc. Trans. 12, 929–932 (1984).

    Article  CAS  PubMed  Google Scholar 

  12. Creighton, T. E., Hillson, D. A. & Freedman, R. B. J. molec. Biol. 142, 43–62 (1980).

    Article  CAS  PubMed  Google Scholar 

  13. Roth, R. A. & Koshland, M. E. Biochemistry 20, 6594–6599 (1981).

    Article  CAS  PubMed  Google Scholar 

  14. Wetlaufer, D. B., Saxena, V. P., Ahmed, A. K., Schaffer, S. W., Pick, P. W., Oh, K.-J. & Peterson, J. D. in Protein Crosslinking Pt A (ed. Friedman, M.) 43–50 (Plenum, New York, 1977).

    Book  Google Scholar 

  15. Teale, J. M. & Benjamin, D. C. J. biol. Chem. 251, 4603–4608 (1976).

    CAS  PubMed  Google Scholar 

  16. Young, R. A. & Davis, R. W. Science 222, 778–782 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Roth, R. A. & Mesirow, M. L. Biochim. biophys. Acta 788, 189–192 (1984).

    Article  CAS  PubMed  Google Scholar 

  18. Hyunh, T., Young, R. & Davis, R. W. in Practical Approaches in Biochemistry (ed. Glover, D.) (IRL, Oxford, in the press).

  19. Paterson, B. M., Roberts, B. E. & Kuff, E. L. Proc. natn. Acad. Sci. U.S.A. 74, 4370–4374 (1977).

    Article  ADS  CAS  Google Scholar 

  20. Reynolds, G. A. et al. Cell 38, 275–285 (1984).

    Article  CAS  PubMed  Google Scholar 

  21. Ohba, H., Harano, T. & Omura, T. J. Biochem., Tokyo 213, 225–234 (1983).

    Google Scholar 

  22. Sabatini, D. D., Kreibich, G., Morimoto, T. & Adesnik, M. J. Cell Biol. 92, 1–22 (1982).

    Article  CAS  PubMed  Google Scholar 

  23. Okada, Y. et al. Eur. J. Biochem. 122, 393–402 (1982).

    Article  CAS  PubMed  Google Scholar 

  24. Ansorge, S. et al. FEBS Lett. 37, 238–240 (1973).

    Article  CAS  PubMed  Google Scholar 

  25. Mills, E. N. C., Lambert, N. & Freedman, R. B. Biochem. J. 213, 245–248 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hillson, D. A. & Freedman, R. B. Biochem. Soc. Trans. 7, 573–574 (1979).

    Article  CAS  PubMed  Google Scholar 

  27. Carmichael, D. F., Keefe, M., Pace, M. & Dixon, J. E. J. biol. Chem. 254, 8386–8390 (1979).

    CAS  PubMed  Google Scholar 

  28. DeLorenzo, F., Fuchs, S. & Anfinsen, C. B. Biochemistry 5, 3961–3965 (1966).

    Article  CAS  Google Scholar 

  29. Holmgren, A., Soderberg, B. O., Eklund, H. & Branden, C. I. Proc. natn. Acad. Sci. U.S.A. 72, 2305–2309 (1975).

    Article  ADS  CAS  Google Scholar 

  30. Finer-Moore, J. & Stroud, R. M. Proc. natn. Acad. Sci. U.S.A. 81, 155–159 (1984).

    Article  ADS  CAS  Google Scholar 

  31. Holmgren, A. J. biol. Chem. 254, 9627–9632 (1979).

    CAS  PubMed  Google Scholar 

  32. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning, A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  33. Aviv, H. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 69, 1408–1412 (1972).

    Article  ADS  CAS  Google Scholar 

  34. Gubler, U. & Hoffman, B. J. Gene 25, 263–269 (1983).

    Article  CAS  PubMed  Google Scholar 

  35. Hanahan, D. J. molec. Biol. 166, 557–580 (1983).

    Article  CAS  PubMed  Google Scholar 

  36. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  37. Hunkapiller, M. W., Hewich, R. M., Dreyer, W. J. & Hood, L. E. Meth. Enzym. 91, 399 (1983).

    Article  CAS  PubMed  Google Scholar 

  38. Hawke, D., Yuan, P. M. & Shively, J. E. Analyt. Biochem. 120, 302 (1982).

    Article  CAS  PubMed  Google Scholar 

  39. Arias, C. F., Lopez, S., Bell, J. R. & Strauss, J. H. J. Virol. 50, 657–661 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Kessler, S. W. J. Immun. 115, 1617–1624 (1975).

    CAS  PubMed  Google Scholar 

  41. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Thomas, P. S. Meth. Enzym. 100, 255–266 (1983).

    Article  CAS  PubMed  Google Scholar 

  43. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5301 (1979).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Edman, J., Ellis, L., Blacher, R. et al. Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin. Nature 317, 267–270 (1985). https://doi.org/10.1038/317267a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/317267a0

This article is cited by

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing