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The folding of hen lysozyme involves partially structured intermediates and multiple pathways

Nature volume 358, pages 302–307 (1992)Cite this article

Abstract

Analysis of the folding of hen lysozyme shows that the protein does not become organized in a single cooperative event but that different parts of the structure become stabilized with very different kinetics. In particular, in most molecules the α-helical domain folds faster than the β-sheet domain. Furthermore, different populations of molecules fold by kinetically distinct pathways. Thus, folding is not a simple sequential assembly process but involves parallel alternative pathways, some of which may involve substantial reorganization steps.

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References

  1. Creighton, T. E. Prog. Biophys. molec. Biol. 33, 231–297 (1978).

    CAS  Article  Google Scholar 

  2. Weissman, J. S. & Kim, P. S. Science 253, 1386–1393 (1991).

    ADS  CAS  Article  Google Scholar 

  3. Schmid, F. X. & Baldwin, R. L. J. molec. Biol. 135, 199–215 (1979).

    CAS  Article  Google Scholar 

  4. Roder, H. & Wüthrich, K. Proteins Struct. Funct. Genet. 1, 34–42 (1986).

    CAS  Article  Google Scholar 

  5. Udgaonkar, J. B. & Baldwin, R. L. Nature 335, 694–699 (1988).

    ADS  CAS  Article  Google Scholar 

  6. Roder, H., Elöve, G. A. & Englander, S. W. Nature 335, 700–704 (1988).

    ADS  CAS  Article  Google Scholar 

  7. Matouschek, A., Kellis, J. T., Serrano, L., Bycroft, M. & Fersht, A. R. Nature 346, 440–445 (1990).

    ADS  CAS  Article  Google Scholar 

  8. Hughson, F. M., Barrick, D. & Baldwin, R. L. Biochemistry 30, 4113–4118 (1991).

    CAS  Article  Google Scholar 

  9. Klemm, J. D., Wozniak, J. A., Alber, T. & Goldenberg, D. P. Biochemistry 30, 589–594 (1991).

    CAS  Article  Google Scholar 

  10. Baum, J., Dobson, C. M., Evans, P. A. & Hanley, C. Biochemistry 28, 7–13 (1989).

    CAS  Article  Google Scholar 

  11. Hughson, F. M., Wright, P. E. & Baldwin, R. L. Science 249, 1544–1548 (1990).

    ADS  CAS  Article  Google Scholar 

  12. Jeng, M.-F., Englander, S. W., Elove, G. A. Wand, J. A. & Roder, H. Biochemistry 29, 10433–10437 (1990).

    CAS  Article  Google Scholar 

  13. Harding, M. M., Williams, D. H. & Woolfson, D. N. Biochemistry 30, 3120–3128 (1991).

    CAS  Article  Google Scholar 

  14. Oas, T. G. & Kim, P. S. Nature 336, 42–47 (1988).

    ADS  CAS  Article  Google Scholar 

  15. Staley, J. P. & Kim, P. S. Nature 334, 685–688 (1990).

    ADS  Article  Google Scholar 

  16. Tanford, C. Adv. Prot. Chem. 24, 1–95 (1970).

    CAS  Google Scholar 

  17. Dobson, C. M. & Evans, P. A. Biochemistry 23, 4267–4270 (1984).

    CAS  Article  Google Scholar 

  18. Kuwajima, K., Hiraoka, Y., Ikeguchi, M. & Sugai, S. Biochemistry 24, 874–881 (1985).

    CAS  Article  Google Scholar 

  19. Ikeguchi, M., Kuwajima, K., Mitani, M. & Sugai, S. Biochemistry 25, 6965–6972 (1986).

    CAS  Article  Google Scholar 

  20. Kato, S., Okamura, M., Shimamoto, N. & Utiyama, H. Biochemistry 20, 1080–1085 (1981).

    CAS  Article  Google Scholar 

  21. Bycroft, M., Matouschek, A., Kellis, J. T. Serrano, L. & Fersht, A. R. Nature 346, 488–490 (1990).

    ADS  CAS  Article  Google Scholar 

  22. Miranker, A., Radford, S. E., Karplus, M. & Dobson, C. M. Nature 349, 633–636 (1991).

    ADS  CAS  Article  Google Scholar 

  23. Wedin, R. E., Delepierre, M., Dobson, C. M. & Poulsen, F. M. Biochemistry 21, 1098–1103 (1982).

    CAS  Article  Google Scholar 

  24. Handoll, H. thesis, Univ. Oxford (1985).

  25. Pederson, T. G. et al. J. molec. Biol. 218, 413–426 (1991).

    ADS  Article  Google Scholar 

  26. Radford, S. E., Buck, M., Topping, K. D., Evans, P. A. & Dobson, C. M. Proteins Struct. Funct. Genet. (in the press).

  27. Udgaonkar, J. B. & Baldwin, R. L. Proc. natn. Acad. Sci. U.S.A. 87, 8197–8201 (1990).

    ADS  CAS  Article  Google Scholar 

  28. Manning, M. C. & Woody, R. W. Biochemistry 28, 8609–8613 (1989).

    CAS  Article  Google Scholar 

  29. Goux, W. J. & Hooker, T. M. Jr Biopolymers 19, 2191–2208 (1980).

    CAS  Article  Google Scholar 

  30. Elöve, G. A., Chaffotte, A. F., Roder, H. & Goldberg, M. E. Biochemistry (in the press).

  31. Robertson, A. D. & Baldwin, R. L. Biochemistry 30, 9907–9914 (1991).

    CAS  Article  Google Scholar 

  32. Jeng, M.-F. & Englander, S. W. J. molec. Biol. 221, 1045–1061 (1991).

    CAS  Article  Google Scholar 

  33. Sugawara, T., Kuwajima, K. & Sugai, S. Biochemistry 30, 2698–2706 (1991).

    CAS  Article  Google Scholar 

  34. Ropson, I. J., Gordon, J. I. & Frieden, C. Biochemistry 29, 9591–9599 (1990).

    CAS  Article  Google Scholar 

  35. Kuwajima, K., Garvey, E. P., Finn, B. E. Matthews, C. R. & Sugai, S. Biochemistry 30, 7693–7703 (1991).

    CAS  Article  Google Scholar 

  36. Brandts, J. F., Halvorson, H. R. & Brennan, M. Biochemistry 14, 4953–4963 (1975).

    CAS  Article  Google Scholar 

  37. Kato, S., Shimamoto, N. & Utiyama, H. Biochemistry 21, 38–43 (1982).

    CAS  Article  Google Scholar 

  38. Schmid, F. X. Biochemistry 22, 4690–4696 (1983).

    CAS  Article  Google Scholar 

  39. Jackson, S. E. & Fersht, A. R. Biochemistry 30, 10436–10443 (1991).

    CAS  Article  Google Scholar 

  40. Elöve, G. A. & Roder, H. Protein Refolding, ACS Symp. Series 470, 50–63 (1991).

    Article  Google Scholar 

  41. Ewbank, J. J. & Creighton, T. E. Nature 350, 518–520 (1991).

    ADS  CAS  Article  Google Scholar 

  42. Briggs, M. S. & Roder, H. Proc. natn. Acad. Sci. U.S.A. 89, 2017–2021 (1992).

    ADS  CAS  Article  Google Scholar 

  43. Kraulis, P. J. J. appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  44. Hvidt, A. A. & Nielsen, S. O. Adv. Prot. Chem. 21, 287–386 (1966).

    CAS  Google Scholar 

  45. Englander, S. W. & Kallenbach, N. R. Q. Rev. Biophys. 16, 521–655 (1984).

    Article  Google Scholar 

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Author information

Affiliations

  1. Oxford Centre for Molecular Sciences and Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, 0X1 3QR, UK

    Sheena E. Radford & Christopher M. Dobson

  2. Cambridge Centre for Molecular Recognition and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK

    Philip A. Evans

Authors
  1. Sheena E. Radford
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  2. Christopher M. Dobson
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  3. Philip A. Evans
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Radford, S., Dobson, C. & Evans, P. The folding of hen lysozyme involves partially structured intermediates and multiple pathways. Nature 358, 302–307 (1992). https://doi.org/10.1038/358302a0

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  • DOI: https://doi.org/10.1038/358302a0

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