Crystal structure of an anti-carbohydrate antibody directed against Vibrio cholerae O1 in complex with antigen: molecular basis for serotype specificity.
The crystal structure of the murine Fab S-20-4 from a protective anti-cholera Ab specific for the lipopolysaccharide Ag of the Ogawa serotype has been determined in its unliganded form and in complex with synthetic fragments of the Ogawa O-specific polysaccharide (O-SP). The upstream terminal O-SP monosaccharide is shown to be the primary antigenic determinant. Additional perosamine residues protrude outwards from the Ab surface and contribute only marginally to the binding affinity and specificity. A complementary water-excluding hydrophobic interface and five Ab-Ag hydrogen bonds are crucial for carbohydrate recognition. The structure reported here explains the serotype specificity of anti-Ogawa Abs and provides a rational basis toward the development of a synthetic carbohydrate-based anti-cholera vaccine.
Villeneuve
S
S
Unité de Biochimie Structurale (Centre National de la Recherche Scientifique, Unité de Recherche Associée 2185), Laboratoire d'Ingénierie des Anticorps, Institut Pasteur, Paris, France.
Souchon
H
H
Riottot
M M
MM
Mazie
J C
JC
Lei
P
P
Glaudemans
C P
CP
Kovác
P
P
Fournier
J M
JM
Alzari
P M
PM
D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012703:Serotyping; D013329:Structure-Activity Relationship; D014734:Vibrio cholerae / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007140:Immunoglobulin Fab Fragments; D008070:Lipopolysaccharides