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Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8433-8.

Crystal structure of an anti-carbohydrate antibody directed against Vibrio cholerae O1 in complex with antigen: molecular basis for serotype specificity.

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  • 1Unité de Biochimie Structurale (Centre National de la Recherche Scientifique, Unité de Recherche Associée 2185), Laboratoire d'Ingénierie des Anticorps, Institut Pasteur, Paris, France.

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.

PMID:
10880560
PMCID:
PMC26965
DOI:
10.1073/pnas.060022997
[PubMed - indexed for MEDLINE]
Free PMC Article
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