The structure and receptor binding properties of the 1918 influenza hemagglutinin

Science. 2004 Mar 19;303(5665):1838-42. doi: 10.1126/science.1093155. Epub 2004 Feb 5.

Abstract

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Birds
  • Crystallography, X-Ray
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
  • History, 20th Century
  • Humans
  • Hydrogen Bonding
  • Influenza A virus / immunology*
  • Influenza A virus / metabolism
  • Influenza A virus / pathogenicity
  • Influenza, Human / epidemiology
  • Influenza, Human / history
  • Influenza, Human / virology*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, Virus / metabolism*
  • Sequence Alignment
  • Sialic Acids / metabolism
  • Species Specificity
  • Swine

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Membrane Glycoproteins
  • Receptors, Virus
  • Sialic Acids
  • hemagglutinin, human influenza A virus

Associated data

  • PDB/1RU7
  • PDB/1RUY
  • PDB/1RUZ
  • PDB/1RV0
  • PDB/1RVT
  • PDB/1RVX
  • PDB/1RVZ