Three-dimensional structure of the Fab fragment of a neutralizing antibody to human rhinovirus serotype 2.
The crystal structure of the antigen-binding fragment of a monoclonal antibody (8F5) that neutralizes human rhinovirus serotype 2 has been determined by X-ray diffraction studies. Antibody 8F5, obtained by immunization with native HRV2 virions, cross-reacts with peptides of the viral capsid protein VP2, which contribute to the neutralizing immunogenic site B in this serotype. The structure was solved by the molecular replacement method and has been refined to an R-factor of 18.9% at 2.8 A resolution. The elbow angle, relating the variable and constant modules of the molecule is 127 degrees, representing the smallest elbow angle observed so far in an Fab fragment. Furthermore, the charged residues of the epitope can be well accommodated in the antigen-binding site. This is the first crystal structure reported for an antibody directed against an icosahedral virus.
Tormo
J
J
Departament d'Enginyeria Química, Escola Tècnica Superior d'Enginyers Industrials, Barcelona, Spain.
Stadler
E
E
Skern
T
T
Auer
H
H
Kanzler
O
O
Betzel
C
C
Blaas
D
D
Fita
I
I
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics; D000914:Antibodies, Viral / Q000737:chemistry* / Q000235:genetics; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D002213:Capsid / Q000276:immunology; D003429:Cross Reactions; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012229:Rhinovirus / Q000145:classification / Q000276:immunology*; D012703:Serotyping; D014771:Virion / Q000276:immunology; D014961:X-Ray Diffraction
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region