Nature 376, 92 - 94 (06 July 2002); doi:10.1038/376092a0

Structure of influenza virus haemagglutinin complexed with a neutralizing antibody

Thierry Bizebard^*, Benoît Gigant^*, Pascal Rigolet^*†, Bjarne Rasmussen^§, Olivier Diat^‡, Peter Böseckei^‡, Steve A. Wharton, John J. Skehel & Marcel Knossow^*

^* Laboratoire de Biologie Structurale, UMR 9920, CNRS-Université Paris-Sud, Bât. 34, CNRS, 91198 Gif-sur-Yvette Cedex, France
^‡ European Synchrotron Radiation Facility, B.P. 220, 38043 Grenoble Cedex, France
^§ European Molecular Biology Laboratory, Grenoble Outstation, c/o I.L.L, B.P. 156, 38042 Grenoble Cedex, France
Division of Virology, M.R.C., National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
^† Present address: Unité de Cristallographie, Bâtiment des protéines, INRA, 78352 Jouy-en-Josas Cedex, France.

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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