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
Wilson, I. A., Skehel, J. J. & Wiley, D. C. Nature 289, 366–373 (1981).
Wiley, D. C. & Skehel, J. J. A. Rev. Biochem. 56, 365–394 (1987).
Weis, W. et al. Nature 333, 426–431 (1988).
Bullough, P. A., Hughson, F. M., Skehel, J. J. & Wiley, D. C. Nature 371, 37–43 (1994).
Ruigrok, R. W., Aitken, A., Calder, L. J. & Markin, S. R. J. gen. Virol., 2785–2795 (1988).
Wharton, S. A. et al. J. biol. Chem. 263, 4474–4480 (1988).
Daniels, R. S., Douglas, A. R., Skehel, J. J. & Wiley, D. C. J. gen. Virol. 64, 1657–1662 (1983).
Daniels, R. S. et al. Cell 40, 431–439 (1985).
Godley, L. et al. Cell 68, 635–645 (1992).
Ruigrok, R. W. et al. EMBO J. 5, 41–49 (1986).
Bizebard, T. et al. Acta crystallogr. D50, 768–777 (1994).
Wrigley, N. G. et al. Virology, 308–314 (1983).
Wilson, I. A. & Stanfield, R. L. Curr. Opin. struct. Biol. 4, 857–867 (1994).
Cherfils, J., Bizebard, T., Knossow, M. & Janin, J. Proteins 18, 8–18 (1994).
Janin, J. & Chothia, C. J. biol. Chem. 265, 16027–16030 (1990).
Wilson, I. A. & Cox, N. J. A. Rev. Immun. 8, 737–771 (1990).
Knossow, M., Daniels, R. S., Douglas, A. R., Skehel, J. J. & Wiley, D. C. Nature 311, 678–680 (1984).
Parry, N. et al. Nature 347, 569–572 (1990).
Skehel, J. J. & Schild, G. C. Virology 44, 396–408 (1971).
Bizebard, T. et al. J. molec. Biol. 216, 513–514 (1990).
Leslie, A. G. W. CCP4 and ESF-EACMB Newsl. Prot. Crystallogr. no. 26 (SERC, Daresbury Lab., Warrington, 1992).
Collaborative Computing Project no. 4 Acta crystallogr. D50, 760–763 (1994).
Navaza, J. Acta Crystallogr. A50, 157–163 (1994).
Jones, T. A. Meth. Enzym. 115, 157–171 (1985).
Brünger, A. T. X-PLOR (version 3.1) Manual (Yale Univ., New Haven, 1992).
Laskowski, R. A., McArthur, M. W., Moss, D. S. & Thornton, J. M. J. appl. Crystallogr. 26, 283–291 (1993).
Shrake, A. & Rupley, J. A. J. molec. Biol. 79, 351–371 (1973).
Ward, C. W. Curr. Top. Microbiol. Immun. 94/95, 1–74 (1981).
Daniels, R. S. et al. EMBO J. 6, 1459–1465 (1987).
Kraulis, P. J. appl. Crystallogr. 24, 924–950 (1991).
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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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DOI: https://doi.org/10.1038/376092a0
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