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Structure of influenza virus haemagglutinin complexed with a neutralizing antibody

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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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Author notes

  1. Pascal Rigolet

    Present address: Unité de Cristallographie, Bâtiment des protéines, INRA, 78352, Jouy-en-Josas Cedex, France

Authors and Affiliations

  1. Laboratoire de Biologie Structurale, UMR 9920, CNRS-Université Paris-Sud, Bât. 34, CNRS, 91198, Gif-sur-Yvette Cedex, France

    Thierry Bizebard, Benoît Gigant, Pascal Rigolet & Marcel Knossow

  2. European Synchrotron Radiation Facility, B.P. 220, 38043, Grenoble Cedex, France

    Olivier Diat & Peter Böseckei

  3. European Molecular Biology Laboratory, Grenoble Outstation, c/o I.L.L, B.P. 156, 38042, Grenoble Cedex, France

    Bjarne Rasmussen

  4. Division of Virology, M.R.C., National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    Steve A. Wharton & John J. Skehel

Authors
  1. Thierry Bizebard
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  2. Benoît Gigant
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  3. Pascal Rigolet
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  4. Bjarne Rasmussen
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  5. Olivier Diat
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  6. Peter Böseckei
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  7. Steve A. Wharton
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  8. John J. Skehel
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  9. Marcel Knossow
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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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