The structure and receptor binding properties of the 1918 influenza hemagglutinin.
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.
Gamblin
S J
SJ
Medical Research Council (MRC) National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Haire
L F
LF
Russell
R J
RJ
Stevens
D J
DJ
Xiao
B
B
Ha
Y
Y
Vasisht
N
N
Steinhauer
D A
DA
Daniels
R S
RS
Elliot
A
A
Wiley
D C
DC
Skehel
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001717:Birds; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism*; D049673:History, 20th Century; D006801:Humans; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D007251:Influenza, Human / Q000453:epidemiology / Q000266:history / Q000821:virology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D016415:Sequence Alignment; D012794:Sialic Acids / Q000378:metabolism; D013045:Species Specificity; D013552:Swine
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D012794:Sialic Acids; C483468:hemagglutinin, human influenza A virus