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Structure of influenza virus haemagglutinin complexed with a neutralizing antibody

Abstract

HAEMAGGLUTININ (HA) is the influenza surface glycoprotein that interacts with infectivity-neutralizing antibodies. As a consequence of this immune pressure, it is the variable virus component, which is important in antigenic drift, that results in recurrent epidemics of influenza. We have determined the crystallographic structure of a complex formed between the antigen-binding fragment (Fab) of a neutralizing antibody and the membrane-distal domain ((HA top9) of a HA subunit prepared from HA in its membrane-fusion-active conformation. A dramatic change is seen in the structure of the Fab-combining site on complex formation. Our results indicate that neutralization of infectivity by this antibody involves the inhibition of receptor binding, and demonstrate how influenza virus can maintain its conserved receptor-binding site despite the immune selective pressure for change in this region of the molecule; they also contribute to a complete description of the endosomal pH-induced fusion-active HA structure.

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References

  1. Wilson, I. A., Skehel, J. J. & Wiley, D. C. Nature 289, 366–373 (1981).

    Article  ADS  CAS  Google Scholar 

  2. Wiley, D. C. & Skehel, J. J. A. Rev. Biochem. 56, 365–394 (1987).

    Article  CAS  Google Scholar 

  3. Weis, W. et al. Nature 333, 426–431 (1988).

    Article  ADS  CAS  Google Scholar 

  4. Bullough, P. A., Hughson, F. M., Skehel, J. J. & Wiley, D. C. Nature 371, 37–43 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Ruigrok, R. W., Aitken, A., Calder, L. J. & Markin, S. R. J. gen. Virol., 2785–2795 (1988).

  6. Wharton, S. A. et al. J. biol. Chem. 263, 4474–4480 (1988).

    CAS  Google Scholar 

  7. Daniels, R. S., Douglas, A. R., Skehel, J. J. & Wiley, D. C. J. gen. Virol. 64, 1657–1662 (1983).

    Article  CAS  Google Scholar 

  8. Daniels, R. S. et al. Cell 40, 431–439 (1985).

    Article  CAS  Google Scholar 

  9. Godley, L. et al. Cell 68, 635–645 (1992).

    Article  CAS  Google Scholar 

  10. Ruigrok, R. W. et al. EMBO J. 5, 41–49 (1986).

    Article  CAS  Google Scholar 

  11. Bizebard, T. et al. Acta crystallogr. D50, 768–777 (1994).

    CAS  Google Scholar 

  12. Wrigley, N. G. et al. Virology, 308–314 (1983).

  13. Wilson, I. A. & Stanfield, R. L. Curr. Opin. struct. Biol. 4, 857–867 (1994).

    Article  CAS  Google Scholar 

  14. Cherfils, J., Bizebard, T., Knossow, M. & Janin, J. Proteins 18, 8–18 (1994).

    Article  CAS  Google Scholar 

  15. Janin, J. & Chothia, C. J. biol. Chem. 265, 16027–16030 (1990).

    CAS  Google Scholar 

  16. Wilson, I. A. & Cox, N. J. A. Rev. Immun. 8, 737–771 (1990).

    Article  CAS  Google Scholar 

  17. Knossow, M., Daniels, R. S., Douglas, A. R., Skehel, J. J. & Wiley, D. C. Nature 311, 678–680 (1984).

    Article  ADS  CAS  Google Scholar 

  18. Parry, N. et al. Nature 347, 569–572 (1990).

    Article  ADS  CAS  Google Scholar 

  19. Skehel, J. J. & Schild, G. C. Virology 44, 396–408 (1971).

    Article  CAS  Google Scholar 

  20. Bizebard, T. et al. J. molec. Biol. 216, 513–514 (1990).

    Article  CAS  Google Scholar 

  21. Leslie, A. G. W. CCP4 and ESF-EACMB Newsl. Prot. Crystallogr. no. 26 (SERC, Daresbury Lab., Warrington, 1992).

    Google Scholar 

  22. Collaborative Computing Project no. 4 Acta crystallogr. D50, 760–763 (1994).

  23. Navaza, J. Acta Crystallogr. A50, 157–163 (1994).

    Article  Google Scholar 

  24. Jones, T. A. Meth. Enzym. 115, 157–171 (1985).

    Article  CAS  Google Scholar 

  25. Brünger, A. T. X-PLOR (version 3.1) Manual (Yale Univ., New Haven, 1992).

    Google Scholar 

  26. Laskowski, R. A., McArthur, M. W., Moss, D. S. & Thornton, J. M. J. appl. Crystallogr. 26, 283–291 (1993).

    Article  CAS  Google Scholar 

  27. Shrake, A. & Rupley, J. A. J. molec. Biol. 79, 351–371 (1973).

    Article  CAS  Google Scholar 

  28. Ward, C. W. Curr. Top. Microbiol. Immun. 94/95, 1–74 (1981).

    Article  Google Scholar 

  29. Daniels, R. S. et al. EMBO J. 6, 1459–1465 (1987).

    Article  CAS  Google Scholar 

  30. Kraulis, P. J. appl. Crystallogr. 24, 924–950 (1991).

    Article  Google Scholar 

Download references

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Bizebard, T., Gigant, B., Rigolet, P. et al. Structure of influenza virus haemagglutinin complexed with a neutralizing antibody. Nature 376, 92–94 (1995). https://doi.org/10.1038/376092a0

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