3UJT

Structure of the Fab fragment of Ab-52, an antibody that binds the O-antigen of Francisella tularensis

Summary for 3UJT

• Entry DOI: 10.2210/pdb3ujt/pdb
• Descriptor: Ab-52 heavy chain, Ab-52 light chain, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: immunoglobulin, immune system, o-antigen
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 4
• Total formula weight: 94002.45

Authors

Rynkiewicz, M.J.,Lu, Z.,Hui, J.H.,Sharon, J.,Seaton, B.A. (deposition date: 2011-11-08, release date: 2012-07-25, Last modification date: 2024-11-20)

Primary citation

Rynkiewicz, M.J.,Lu, Z.,Hui, J.H.,Sharon, J.,Seaton, B.A.
Structural Analysis of a Protective Epitope of the Francisella tularensis O-Polysaccharide.
Biochemistry, 51:5684-5694, 2012

PubMed Abstract: 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, α-D-GalpNAcAN(1→4)-α-D-GalpNAcAN(1→3)-β-D-QuipNAc(1→2)-β-D-Quip4NFm(1→4)-α-D-GalpNAcAN(1→4)-α-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.

PubMed: 22747335
DOI: 10.1021/bi201711m

Experimental method

X-RAY DIFFRACTION (2.1 Å)