Skip to main content
SpringerLink
Log in

Improvement in the oxidative folding of endothelin-1 by a lys-Arg extension at the amino terminus: Implication of a salt bridge between Arg−1 and Asp8

  • Published:
Letters in Peptide Science Aims and scope Submit manuscript

Summary

An amino-terminal extension of endothelin-l by the lys-Arg dipeptide in the prosequence (KR-ET-1) greatly increased the ratio of native-type to non-native-type disulfide isomer (96/4 versus 71/29) during the oxidative folding reaction. This improvement was completely abolished by substituting Asn for Asp at position 8 (D8N-KR-ET-1), whereas most of it was maintained with similar carboxamide analogues replaced at Glu10 or Asp18. Structure analyses by circular dichroism spectroscopy revealed that (i) in the carboxylate state, the α-helical content of the native-type isomer of KR-ET-l is higher than that of the native-type isomer of ET-1, while such a variation is not observed in the corresponding non-native-type isomer of KR-ET-l; and (ii) the enhanced α-helicity resulting from the Lys-Arg extension is largely diminished in D8N-KR-ET-l. From these results and our previous findings that the helical structure in KR-ET-l is stabilized by a particular salt bridge between the extended Arg−1 basic moiety and either the Asp8 or Glu10 acidic side chain in Et-1 [Aumelas, A. et al., Biochemistry, 34 (1995) 4546], we conclude that the formation of a specific salt bridge between the side chains of Arg−1 and Asp8 in KR-ET-1 is critical for the predominant generation of the native-type disulfide isomer, probably because it stabilizes the helical structure of parental ET-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K. and Masaki, T., Nature, 332 (1988) 411.

    Article  PubMed  CAS  Google Scholar 

  2. Kumagaye, S., Kuroda, H., Nakajima, K., Watanabe, T.X., Kimura, T., Masaki, T. and Sakakibara, S., Int. J. Pept. Protein Res., 32 (1988) 519.

    Article  PubMed  CAS  Google Scholar 

  3. Itoh, Y., Yanagisawa, M., Ohkubo, S., Kimura, C., Kosaka, T., Inoue, A., Ishida, N., Mitsui, Y., Onda, H., Fujino, M. and Masaki, T., FEBS Lett. 231 (1988) 440.

    Article  PubMed  CAS  Google Scholar 

  4. Kitada, C., Tanaka, E. and Fujino, M., In Shimonishi, Y. (Ed.) Peptide Chemistry 1990, Protein Research Foundation, Osaka, Japan, 1991, pp. 405–408.

    Google Scholar 

  5. Galantino, M., de Castiglione, R., Cristiani, C., Vaghi, F., Liu, W., Zhang, J.-W and Tam, J.P., Pept. Res. 8 (1995) 154.

    PubMed  CAS  Google Scholar 

  6. Nomizu, M., Inagaki, Y., Iwamatsu, A., Kashiwabara, T., Ohta, H., Morita, A., Nishikori, K., Otaka, A., Fujii, N. and Roller, P.P., Int. J. Pept. Protein Res., 38 (1991) 580.

    Article  PubMed  CAS  Google Scholar 

  7. Nakajima, K., Kubo, S., Kumagaye, S., Nishio, H., Tsunemi, M., Inui, T., Kuroda, H., Chino, N., Watanabe, T.X., Kimura, T. and Sakakibara, S., Biochem Biophys. Res. Commun., 163 (1989) 424.

    Article  PubMed  CAS  Google Scholar 

  8. Aumelas, A., Chiche, L., Kubo, S., Chino, N., Tamaoki, H. and Kobayashi, Y., Biochemistry, 34 (1995) 4546.

    Article  PubMed  CAS  Google Scholar 

  9. Tamaoki, H., Kobayashi, Y., Nishimura, S., Ohkubo, T., Kyogoku, Y., Nakajima, K., Kumagaye, S., Kimura, T. and Sakakibara, S., Protein Eng., 4 (1991) 509.

    PubMed  CAS  Google Scholar 

  10. Aumelas, A., Chiche, L., Mahe, E., Le-Nguyen, D., Sizum, P., Berthault, P. and Perly, B., Int. J. Pept. Protein Res., 37 (1991) 315.

    Article  PubMed  CAS  Google Scholar 

  11. Anderson, N.H., Chen, C., Marchner, T.M., Krystek Jr., S.R. and Bassolino, D.A., Biochemistry. 31 (1992) 1280.

    Article  Google Scholar 

  12. Creighton, T.E., J. Mol. Biol., 144 (1980) 521.

    Article  PubMed  CAS  Google Scholar 

  13. Moroder, L., Besse, D., Musiol, H.-J., Rudolph-Böhner, S. and Siedler, F., Biopolymers, 40 (1996) 207.

    Article  PubMed  CAS  Google Scholar 

  14. Kubo, S., Chino, N., Watanabe, T.X., Kimura, T. and Sakakibara, S., Pept. Res., 6 (1993) 66.

    PubMed  CAS  Google Scholar 

  15. Kubo, S., Chino, N., Kimura, T. and Sakakibara, S., Biopolymers 38 (1996) 733.

    Article  PubMed  CAS  Google Scholar 

  16. Ikemura, H., Takagi, H. and Inouye, M., J. Biol. Chem., 262 (1987) 7859.

    PubMed  CAS  Google Scholar 

  17. Shinde, U., Li, Y., Chatterjee, S. and Inouye, M., Proc. Natl. Acad. Sci. USA, 90 (1993) 6924.

    Article  PubMed  CAS  Google Scholar 

  18. Silen, J.L. and Agard, D.A., Nature, 341 (1989) 362.

    Article  Google Scholar 

  19. Winther, J.R. and Sorensen, P., Proc. Natl. Acad. Sci. USA, 88 (1991) 9330.

    Article  PubMed  CAS  Google Scholar 

  20. Weissman, J.S. and Kim, P.S., Cell, 71 (1992) 841.

    Article  PubMed  CAS  Google Scholar 

  21. Ohashi, H., Katsuta-Enomoto, Y., Yasufuku, K., Okada, K. and Yano, M., J. Biochem., 110 (1991) 628.

    PubMed  CAS  Google Scholar 

  22. Tam, J.P., Dong, X. and Wu, C.-R., In Yanaihara, N. (Ed.) Peptide Chemistry 1992 (Proceedings of the 2nd Japan Symposium on Peptide Chemistry), ESCOM, Leiden, The Netherlands, 1993, pp. 24–26.

Download references

Author information

Author notes

  1. Haruhiko Tamaoki

    Present address: Department of Biochemistry, Kumamoto University School of Medicine, 2-2-1 Honjo, 860, Kumamoto, Japan

Authors and Affiliations

  1. Protein Research Foundation, Peptide Institute, Inc., 4-1-2 Ina, Minoh, 562, Osaka, Japan

    Shigeru Kubo, Naoyoshi Chino, Kiichiro Nakajima, Terutoshi Kimura & Shumpei Sakakibara

  2. Faculté de Pharmacie, Centre de Biochimie Structurale CNRS UMR C9955, INSERM U414, F-34060, Montpellier Cedex 1, France

    André Aumelas & Laurent Chiche

  3. Department of Physics, School of Science, Kwansei Gakuin University, 662, Nishinomiya, Japan

    Shin-ichi Segawa

  4. Institute for Protein Research and Faculty of Pharmaceutical Sciences, Osaka University, 565, Suita Osaka, Japan

    Haruhiko Tamaoki & Yuji Kobayashi

Authors
  1. Shigeru Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoyoshi Chino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiichiro Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. André Aumelas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurent Chiche
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shin-ichi Segawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Haruhiko Tamaoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuji Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Terutoshi Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shumpei Sakakibara
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kubo, S., Chino, N., Nakajima, K. et al. Improvement in the oxidative folding of endothelin-1 by a lys-Arg extension at the amino terminus: Implication of a salt bridge between Arg−1 and Asp8 . Lett Pept Sci 4, 185–192 (1997). https://doi.org/10.1007/BF02443532

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02443532

Keywords

Search

Navigation