Crystal structure of ovalbumin as a model for the reactive centre of serpins (original) (raw)

Nature volume 347, pages 99–102 (1990)Cite this article

Abstract

THE serpins are a widely distributed family of proteins with diverse functions; they include the key serine protease inhibitors of human plasma as well as noninhibitory homologues such as hormone-binding globulins, angiotensinogen and egg-white ovalbumin1. Sequence alignment based on the crystal structure of the cleaved form of the archetypal serpin, a α1-antitrypsin2, indicates that the serpins share a common highly ordered structure3. On cleavage of the reactive centre peptide bond, they characteristically undergo a remarkable conformational change, the newly generated C ter-minus moving some 70 Å to the opposite pole of the molecule. The structure of this post-cleavage form is known, but the conformation of the intact serpins and in particular that of their reactive centre is not. Wright et al.'s structure of plakalbumin4 (ovalbumin cleaved by subtilisin) has provided evidence for the conformational change that results from cleavage. We have now determined the structure of native ovalbumin to 1.95 Å resolution and have found that the intact peptide loop forming the analogue to the reactive centre of the inhibitory serpins takes the unexpected form of a protruding, isolated helix. This model of the intact structures of the serpins suggests how they may interact with their target proteases.

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References

  1. Hunt, L. T. & Dayhoff, M. O. Biochem. biophys. Res. Commun. 95, 864–871 (1980).
    Article CAS Google Scholar
  2. Löebermann, H., Tokuoka, R., Deisenhofer, J. & Huber, R. J. molec. Biol. 177, 531–556 (1984).
    Article Google Scholar
  3. Huber, R. & Carrell, R. W. Biochemistry 28, 8951–8966 (1989).
    Article CAS Google Scholar
  4. Wright, H. T., Qian, H. X. & Huber, R. J. molec. Biol. 213, 513–518 (1990).
    Article CAS Google Scholar
  5. Carrell, R. W. & Owen, M. C. Nature 317, 730–732 (1985).
    Article ADS CAS Google Scholar
  6. Pemberton, P. A., Stein, P. E., Pepys, M. B., Potter, J. M. & Carrell, R. W. Nature 336, 257–258 (1988).
    Article ADS CAS Google Scholar
  7. Gettins, P. J. biol. Chem. 264, 3781–3785 (1989).
    CAS PubMed Google Scholar
  8. Stein, P. E., Tewkesbury, D. A. & Carrell, R. W. Biochem. J. 262, 103–107 (1989).
    Article CAS Google Scholar
  9. Linderstrøm-Lang, K. & Ottesen, M. C. r. Trav. Lab. Carlsberg 26, 403–442 (1949).
    Google Scholar
  10. Wright, H. T. J. biol. Chem. 259, 14335–14336 (l984).
    Google Scholar
  11. Perry, D. J. & Carrell, R. W. Molec. Biol. Med. 6, 239–243 (1989).
    CAS PubMed Google Scholar
  12. Levy, N. X., Ramesh, N., Cicardi, M., Harrison, R. A. & Davis, A. E. Proc. natn. Acad. Sci. U.S.A. 87, 265–268 (1990).
    Article ADS CAS Google Scholar
  13. McPhalen, C. A. & James, M. N. G. Biochemistry 26, 261–269 (1987).
    Article CAS Google Scholar
  14. Bode, W., Papamokos, E., Musil, D., Seemueller, U. & Fritz, H. EMBO J. 5, 813–818 (1986).
    Article CAS Google Scholar
  15. Ptitsyn, O. B. Pure Appl. Chem. 31, 227–244 (1972).
    Article CAS Google Scholar
  16. Warner, R. C. in The Proteins Vol. 2a (eds Neurath, H. & Bailey, K.) 435–485 (Academic, New York, 1954).
    Book Google Scholar
  17. Goux, W. J. & Venkatasoubramanian, P. N. Biochemistry 25, 84–94 (1986).
    Article CAS Google Scholar
  18. Miller, M., Weinstein, J. N. & Wlodawer, A. J. biol. Chem. 258, 5864–5866 (1983).
    CAS PubMed Google Scholar
  19. Sussmann, J. L., Holbrook, S. R., Church, G. M. & Kim, S.-H. Acta crystallogr. A33, 800–804 (1977).
    Article Google Scholar
  20. Brünger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).
    Article ADS Google Scholar
  21. Hendrickson, W. A. & Konnert, J. H. in Computing in Crystallography (eds Diamond, R., Ramaseshan, S. & Venkatesan, K.) 13.01–13.23 (Indian Institute of Science, Bangalore, 1980).
    Google Scholar
  22. Jones, T. A., J. appl. Crystallogr. 11, 268–272 (1978).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Department of Haematology, University of Cambridge, Hills Road, Cambridge, CB2 2QH, UK
    Penelope E. Stein & Robin W. Carrell
  2. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
    Andrew G. W. Leslie, John T. Finch, William G. Turnell & Paul J. McLaughlin

Authors

  1. Penelope E. Stein
  2. Andrew G. W. Leslie
  3. John T. Finch
  4. William G. Turnell
  5. Paul J. McLaughlin
  6. Robin W. Carrell

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Stein, P., Leslie, A., Finch, J. et al. Crystal structure of ovalbumin as a model for the reactive centre of serpins.Nature 347, 99–102 (1990). https://doi.org/10.1038/347099a0

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