Structure of influenza virus haemagglutinin complexed with a neutralizing antibody.
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 top') 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.
Bizebard
T
T
Laboratoire de Biologie Structurale, UMR 9920, CNRS-Université Paris-Sud, Gif-sur-Yvette, France.
Gigant
B
B
Rigolet
P
P
Rasmussen
B
B
Diat
O
O
Bösecke
P
P
Wharton
S A
SA
Skehel
J J
JJ
Knossow
M
M
D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007140:Immunoglobulin Fab Fragments