Nature 333, 426 - 431 (02 June 1988); doi:10.1038/333426a0

Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid

W. Weis^*£, J. H. Brown^*, S. Cusack^*£, J. C. Paulson^†, J. J. Skehel^‡ & D. C. Wiley^*§

^*Depaortment of Biochemistry and Molecular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA
^†Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90024, USA
^‡National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
^§To whom correspondence should be addressed.
^£Present addresses: EMBL, c/o I.L.L., 156x, 38042 Grenoble Cedex, France (S.C.); Department of Molecular Biophysics and Biochemistry and Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06511, USA (W.W.).

The three-dimensional structures of influenza virus haemagglutinins complexed with cell receptor analogues show sialic acids bound to a pocket of conserved amino acids surrounded by antibody-binding sites. Sialic acid fills the conserved pocket, demonstrating that it is the influenza virus receptor. The proximity of the antibody-binding sites suggests that antibodies neutralize virus infectivity by preventing virus-to-cell binding. The structures suggest approaches to the design of anti-viral drugs that could block attachment of viruses to cells.

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