Docking of a human rhinovirus neutralizing antibody onto the viral capsid.
The structure of the complex between the Fab fragment of a human rhinovirus serotype 2 (HRV2) neutralizing antibody (8F5) and a cross-reactive synthetic peptide derived from the viral capsid protein VP2 has been recently determined by crystallographic methods. The conformation adopted by the peptide was very similar to and could be superimposed onto the corresponding region of the viral protein VP2 of human rhinovirus 1A (HRV1A) whose three-dimensional structure is known. The structure of the Fab fragment determined in the complex was docked onto the viral capsid using the superimposition transformation found for the peptide. In the resulting model the Fab protrudes almost radially to about 60 A from the surface of the virion without any major steric problem. The Fab fragment was then placed on each one of the 60 equivalent epitopes using the T = 1 icosahedral symmetry of the virus. The closest pairs of Fab fragments are related by viral 2-fold axes and run almost parallel to each other without clashing. These axes of symmetry from the viral particle could thus be coincident with the dyad axes of the antibodies. Furthermore, comparison of the three-dimensional structure of the Fab/peptide complex with the structure of the Fab fragment alone indicates that the flexibility of the antibody's elbow would facilitate bivalent attachment to the same viral particle. In accordance with the docking results, experimental determination of the stoichiometry of binding yielded a ratio of 30 IgG molecules per virion also suggesting bivalent attachment of antibody 8F5 onto the viral particle. The neutralization of viral infectivity, being neither aggregation (this paper) nor inhibition of receptor binding, might be mainly achieved by reducing viral spread from cell to cell and/or inhibition of uncoating.
Tormo
J
J
Institute of Biochemistry, University of Vienna, Austria.
Centeno
N B
NB
Fontana
E
E
Bubendorfer
T
T
Fita
I
I
Blaas
D
D
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000737:chemistry* / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002213:Capsid / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D036022:Capsid Proteins; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012229:Rhinovirus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*
D000914:Antibodies, Viral; D036022:Capsid Proteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; C442544:VP2 protein, Rhinovirus