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Publication Abstract from PubMed

Francisella tularensis (Ft), the Gram-negative facultative intracellular bacterium that causes tularemia, is considered a biothreat because of its high infectivity and the high mortality rate of respiratory disease. The Ft lipopolysaccharide (Ft LPS) is thought to be a main protective antigen in mice and humans, and we have previously demonstrated the protective effect of the Ft LPS-specific monoclonal antibody Ab52 in a mouse model of respiratory tularemia. Immunochemical characterization has shown that the epitope recognized by Ab52 is contained within two internal repeat units of the O-polysaccharide [O-antigen (OAg)] of Ft LPS. To further localize the Ab52 epitope and understand the molecular interactions between the antibody and the saccharide, we determined the X-ray crystal structure of the Fab fragment of Ab52 and derived an antibody-antigen complex using molecular docking. The docked complex, refined through energy minimization, reveals an antigen binding site in the shape of a large canyon with a central pocket that accommodates a V-shaped epitope consisting of six sugar residues, alpha-d-GalpNAcAN(1-->4)-alpha-d-GalpNAcAN(1-->3)-beta-d-QuipNAc(1-->2)-beta-d-Qu ip4NFm(1-->4)-alpha-d-GalpNAcAN(1-->4)-alpha-d-GalpNAcAN. These results inform the development of vaccines and immunotherapeutic/immunoprophylactic antibodies against Ft by suggesting a desired topology for binding of the antibody to internal epitopes of Ft LPS. This is the first report of an X-ray crystal structure of a monoclonal antibody that targets a protective Ft B cell epitope.

Structural Analysis of a Protective Epitope of the Francisella tularensis O-Polysaccharide.,Rynkiewicz MJ, Lu Z, Hui JH, Sharon J, Seaton BA Biochemistry. 2012 Jul 2. PMID:22747335^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.