Three-dimensional structures of influenza virus neuraminidase-antibody complexes.
X-ray diffraction analysis of crystals of a monoclonal Fab fragment NC41 bound to a viral antigen, influenza virus neuraminidase, shows an epitope involving five surface loops of the antigen. In addition it reveals an unusual pairing pattern between the domains of light and heavy chains in the variable module of the antibody. We interpret this result to imply that association with antigen can induce changes in the quaternary structure of the Fab, through a sliding of domains at the variable light/variable heavy chains (VL-VH) interface. In addition, Fab binding has altered the conformation of some of the surface loops of the antigen. The structure of the NC10 Fab-neuraminidase complex has now also been solved. It binds an epitope that overlaps the NC41 epitope. In this structure, there is no electron density for the C-module of the Fab fragment, implying it is disordered in the crystal lattice. The implications of these, and other antibody-antigen structures, for immune recognition are discussed.
Colman
P M
PM
CSIRO Division of Biotechnology, Parkville, Victoria, Australia.
Tulip
W R
WR
Varghese
J N
JN
Tulloch
P A
PA
Baker
A T
AT
Laver
W G
WG
Air
G M
GM
Webster
R G
RG
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D046911:Macromolecular Substances; D008958:Models, Molecular; D009439:Neuraminidase / Q000276:immunology; D009975:Orthomyxoviridae / Q000201:enzymology; D011487:Protein Conformation; D014961:X-Ray Diffraction
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D046911:Macromolecular Substances; D009439:Neuraminidase