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:

Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins

Abstract

The enzyme peptidyl-prolyl cis-trans isomerase (PPIase) was recently discovered in mammalian tissues and purified from porcine kidney1. It catalyses the slow cis-trans isomerization of proline peptide (Xaa-Pro) bonds in oligopeptides and accelerates slow, rate-limiting steps in the folding of several proteins2-5. Here, we report the N-terminal sequence of PPIase together with further chemical and enzymatic properties. The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA). Cyclophilin is thought to be linked to the immunosuppressive action of CsA6-11. The first 38 amino-acid residues of porcine PPIase and of bovine cyclophilin are identical and the two proteins both have a relative molecular mass of about 17,000 (ref. 7). The catalysis of prolyl isomerization in oligopeptides and of protein folding by PPIase are strongly inhibited in the presence of low levels of CsA. The activities of both PPIase and cyclophilin depend on a single sulphydryl group. At present it is unknown whether the inhibition of prolyl isomerase activity is related with the immunosuppressive action of CsA.

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. Fischer, G., Bang, H. & Mech, C. Biomed. biochim. Acta 43, 1101–1111 (1984).

    CAS  Google Scholar 

  2. Fischer, G. & Bang, H. Biochim. biophys. Acta 828, 39–42 (1985).

    Article  CAS  Google Scholar 

  3. Lang, K., Schmid, F. X. & Fischer, G. Nature 329, 268–270 (1987).

    Article  ADS  CAS  Google Scholar 

  4. Lang, K. & Schmid, F. X. Nature 331, 453–455 (1988).

    Article  ADS  CAS  Google Scholar 

  5. Bächinger, H. P. J. biol Chem. 262, 17144–17148 (1987).

    PubMed  Google Scholar 

  6. Handschumacher, R. E., Harding, M. W., Rice, J., Drugge, R. J. & Speicher, D. W. Science 226, 544–547 (1984).

    Article  ADS  CAS  Google Scholar 

  7. Harding, M. W., Handschumacher, R. E. & Speicher, D. W. J. biol. Chem. 261, 8547–8555 (1986).

    CAS  Google Scholar 

  8. Dalgarno, D. C., Harding, M. W. Lazarides, A., Handschumacher, R. E. & Armitage, I. M. Biochemistry 25, 6778–6784 (1986).

    Article  CAS  Google Scholar 

  9. Koletsky, A. J., Harding, M. W. & Handschumacher, R. E. J. Immun. 137, 1054–1059 (1986).

    CAS  PubMed  Google Scholar 

  10. Haendler, B., Hofer-Warbinek, R. & Hofer, E. EMBO J. 6, 947–950 (1987).

    Article  CAS  Google Scholar 

  11. Danielson, P. E. et al. DNA 7, 261–268 (1988).

    Article  CAS  Google Scholar 

  12. Edelhoch, H. Biochemistry 6, 1948–1954 (1967).

    Article  CAS  Google Scholar 

  13. Payot, P. Eur. J. Biochem. 63, 263–269 (1976).

    Article  Google Scholar 

  14. Fischer, G. & Bang, H. in Functional and Regulatory Aspects of Enzyme Action (ed. Helmreich, E. J. M.) (J. A. Barth, Leipzig, in the press).

  15. Lang, K. Thesis, Regensburg, 1988.

  16. Krönke, M. et al. Proc. natn. Acad. Sci. U.S.A. 81, 5214–5218 (1984).

    Article  ADS  Google Scholar 

  17. Fischer, G., Bang, H., Berger, E. & Schellenberger, A. Biochim biophys. Acta 791, 87–97 (1984).

    Article  CAS  Google Scholar 

  18. Boyer, P. D. J. Am. chem. Soc. 76, 4331–4335 (1954).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fischer, G., Wittmann-Liebold, B., Lang, K. et al. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337, 476–478 (1989). https://doi.org/10.1038/337476a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/337476a0

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