Structure of a neutralizing antibody bound bivalently to human rhinovirus 2.
The structure of a complex between human rhinovirus serotype 2 (HRV2) and the weakly neutralizing monoclonal antibody 8F5 has been determined to 25 A resolution by cryo-electron microscopy and 3-D reconstruction techniques. THe antibody is seen to be bound bivalently across the icosahedral 2-fold axis, despite the very short distance of 60 A between the symmetry-related epitopes. The canyon around the 5-fold axis is not obstructed. Due to extreme flexibility of the hinge region the Fc domains occupy random orientations and are not visible in the reconstruction. The atomic coordinates of Fab-8F5 complexes with a synthetic peptide derived from the viral protein 2 (VP2) epitope were fitted to the structure obtained by cryo-electron microscope techniques. The X-ray structure of HRV2 is not unknown, so that of the closely related HRV1A was placed in the electron microscopic density map. The footprint of 8F5 on the viral surface is largely on VP2, but also covers the VP3 loop centred on residue 3060. C alpha atoms of VP1 and 8F5 come no closer than 10 A. Based on the fit of the X-ray coordinates to the electron microscope data, the synthetic 15mer peptide starts and ends in close proximity to the corresponding amino acids of VP2 on HRV1A. However, the respective loops diverge considerably in their overall spatial disposition. It appears from this study that bivalent binding of an antibody directed against a picornavirus exists for a smaller spanning distance than was previously thought possible. Also bivalent binding does not ensure strong neutralization.
Hewat
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Institut de Biologie Structurale Jean-Pierre Ebel, Grenoble, France.
Blaas
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000648:ultrastructure; D000914:Antibodies, Viral / Q000737:chemistry* / Q000648:ultrastructure; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008958:Models, Molecular; D015394:Molecular Structure; D009500:Neutralization Tests; D012229:Rhinovirus / Q000145:classification / Q000276:immunology*; D012703:Serotyping
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex