Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus.
The 1918 "Spanish" influenza pandemic represents the largest recorded outbreak of any infectious disease. The crystal structure of the uncleaved precursor of the major surface antigen of the extinct 1918 virus was determined at 3.0 angstrom resolution after reassembly of the hemagglutinin gene from viral RNA fragments preserved in 1918 formalin-fixed lung tissues. A narrow avian-like receptor-binding site, two previously unobserved histidine patches, and a less exposed surface loop at the cleavage site that activates viral membrane fusion reveal structural features primarily found in avian viruses, which may have contributed to the extraordinarily high infectivity and mortality rates observed during 1918.
Stevens
James
J
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Corper
Adam L
AL
Basler
Christopher F
CF
Taubenberger
Jeffery K
JK
Palese
Peter
P
Wilson
Ian A
IA
D000595:Amino Acid Sequence; D001665:Binding Sites; D002236:Carbohydrate Conformation; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D049673:History, 20th Century; D006801:Humans; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D007251:Influenza, Human / Q000453:epidemiology / Q000266:history / Q000821:virology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D012794:Sialic Acids; C109963:hemagglutinin, avian influenza A virus; C483468:hemagglutinin, human influenza A virus; D006639:Histidine