title: Crystal structure of an anti-carbohydrate antibody directed against Vibrio cholerae O1 in complex with antigen: molecular basis for serotype specificity.
abstract: 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.
authors.affiliation: Unité de Biochimie Structurale (Centre National de la Recherche Scientifique, Unité de Recherche Associée 2185), Laboratoire d'Ingénierie des Anticorps, Institut Pasteur, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Villeneuve
authors.forename: H
authors.initials: H
authors.lastname: Souchon
authors.forename: M M
authors.initials: MM
authors.lastname: Riottot
authors.forename: J C
authors.initials: JC
authors.lastname: Mazie
authors.forename: P
authors.initials: P
authors.lastname: Lei
authors.forename: C P
authors.initials: CP
authors.lastname: Glaudemans
authors.forename: P
authors.initials: P
authors.lastname: Kovác
authors.forename: J M
authors.initials: JM
authors.lastname: Fournier
authors.forename: P M
authors.initials: PM
authors.lastname: Alzari
mesh_terms: 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*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007140:Immunoglobulin Fab Fragments; D008070:Lipopolysaccharides