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.

  • Review Article
  • Published:

Kinetic studies of protein folding using NMR spectroscopy

Nature Structural Biology volume 5, pages 504–507 (1998)Cite this article

Abstract

Recent progress has advanced our abilities to use NMR spectroscopy to follow -- in real time -- the structural and dynamic changes taking place during protein folding.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Stopped-flow 19F NMR spectra of the refolding of 6-19F-tryptophan labeled Escherichia coli dihydrofolate reductase following dilution from 5.5 to 2.75 M urea at 5 °C in the presence of 3.8 mM NADP+.
Figure 2: NMR folding profiles of a peptide (top) labeled with 15N at Gly 24 (circles) and Ala 13 (squares). O is the one-letter amino acid code for hydroxyproline.
Figure 3: 1H photo-CIDNP spectra (B) of the refolding of hen lysozyme after a simultaneous pH jump from 1.1 to 5.2, and dilution from 10 to 1.4 M urea17.
Figure 4: (1H-15N) HSQC spectra of bovine α-lactalbumin at 3 °C during different stages of the folding process.

Similar content being viewed by others

References

  1. Dobson, C.M., Sali, A. & Karplus, M. Angew. Chem. Int. Ed. Eng. 37, 868–893 (1998).

    Article  Google Scholar 

  2. Smith, L.J., Fiebig, K.M., Schwalbe, H. & Dobson, C.M. Folding & Design 1, 95–106 (1996).

    Article  Google Scholar 

  3. Plaxco, K. & Dobson, C.M. Curr. Opin. Struct. Biol. 6, 630–636 (1996).

    Article  CAS  Google Scholar 

  4. Baldwin, R.L. Curr. Opin. Struct. Biol. 3, 84–91 (1993).

    Article  CAS  Google Scholar 

  5. Grimaldi, J.J., Baldo, J., McMurray, C. & Sykes, B.D. J. Amer. Chem. Soc. 94, 7641–7645 ( 1972).

    Article  CAS  Google Scholar 

  6. Grimaldi, J.J. & Sykes, B.D. Rev. Sci. Instr. 46, 1201–1205 (1975).

    Article  Google Scholar 

  7. van Nuland, N.A.J., Forge, V., Balbach, J. & Dobson, C.M. Accts. Chem. Res,, in the press.

  8. Frieden, C., Hoetzli, S.D. & Ropson, I.J. Prot. Sci. 2, 2007– 2014 (1993).

    Article  CAS  Google Scholar 

  9. Hoetzli, S.D. & Frieden, C. Biochemistry 35, 16843–16851 (1996).

    Article  Google Scholar 

  10. Hoetzli, S.D. & Frieden, C. Biochemistry 37, 387–398 (1998).

    Article  Google Scholar 

  11. Liu, X., Siegel, D.L., Fan, P., Brodsky, B. & Baum, J. Biochemistry 35, 4306– 4313 (1996).

    Article  CAS  Google Scholar 

  12. Baum, J. & Brodsky, B. Folding & Design 2, R53–R60 (1997).

    Article  CAS  Google Scholar 

  13. Pascher, T., Chesick, J.P., Winkler, J.R. & Gray, H.B Science 271, 1558–1560 ( 1996).

    Article  CAS  Google Scholar 

  14. Telford, J.R., Wittung-Stafshede, P., Gray, H.B. & Winkler, J.R. Acc. Chem. Res. (1998) in the press.

  15. Dobson, C.M., Evans, P.A. & Radford, S.E. Trends Biochem. Sci. 19, 31 –37 (1994).

    Article  CAS  Google Scholar 

  16. Kuwajima, K. FASEB J. 10, 102–109 ( 1996).

    Article  CAS  Google Scholar 

  17. Hore P.J., Winder S.L., Roberts, C.H. & Dobson, C.M. J. Amer. Chem. Soc. 119, 5049–5050 (1997).

    Article  CAS  Google Scholar 

  18. Hore, P.J. & Broadhurst, R.W. Prog. NMR Spec. 25, 345–402 (1993).

    Article  CAS  Google Scholar 

  19. Broadhurst, R.W., Dobson, C.M., Hore, P.J., Radford, S.E. & Rees, M.L. Biochemistry 30, 405– 412 (1991).

    Article  CAS  Google Scholar 

  20. Balbach, J. et al. Nature Struct. Biol. 2, 865– 870 (1995).

    Article  CAS  Google Scholar 

  21. Balbach, J. et al. Science 274, 1161– 1163 (1996).

    Article  CAS  Google Scholar 

  22. Balbach, J. et al. Proc. Natl Acad. Sci. USA 94, 7182– 7185 (1997).

    Article  CAS  Google Scholar 

  23. Nölting, B., Golbik, R. & Fersht, A.R. Proc. Natl. Acad. Sci. USA 92, 10668–10672 (1995).

    Article  Google Scholar 

  24. Dyson, H.J. & Wright, P.E. Nature Struct. Biol. 5, 499–503 (1998).

    Article  CAS  Google Scholar 

  25. Schulman, B., Kim, P.S., Dobson, C.M. & Redfield, C. Nature Struct. Biol. 4, 630–634 ( 1997).

    Article  CAS  Google Scholar 

  26. Huang, G.S. & Oas, T.G. Proc. Natl. Acad. Sci. USA 92, 6878–6882 (1995).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Acknowledgments

We thank J. Balbach, V. Forge, J. A. Jones, N. A. J. van Nuland and S. L. Winder, for many of the ideas that have gone into the work from our own laboratories and that is discussed here. We are grateful to J. Baum, H. B. Gray, R. Kaptein and J. Balbach for kindly providing reprints of unpublished work, and to C. Freiden and J. Baum for copies of Figs 1 and 2. The Oxford Centre for Molecular Sciences is supported by BBSRC, EPSRC and MRC. The research of C.M.D. is also supported by the Howard Hughes Medical Institute and the Wellcome Trust.

Author information

Authors and Affiliations

  1. Oxford Centre for Molecular Sciences, New Chemistry Laboratory, Oxford, OX1 3QR, South Parks Road, UK

    Christopher M. Dobson & Peter J. Hore

  2. Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QR, South Parks Road, UK

    Christopher M. Dobson & Peter J. Hore

Authors
  1. Christopher M. Dobson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. Hore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Christopher M. Dobson or Peter J. Hore.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dobson, C., Hore, P. Kinetic studies of protein folding using NMR spectroscopy. Nat Struct Mol Biol 5 (Suppl 7), 504–507 (1998). https://doi.org/10.1038/744

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/744

This article is cited by

Search

Advanced 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