Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: tularemia [ICD11:
1B94 
, ICD11:
XN0BX ];
infection due to Francisella tularensis [ICD11:
XN0BX ]
NCBI PubMed ID: 22747335Publication DOI: 10.1021/bi201711mJournal NLM ID: 0370623Publisher: American Chemical Society
Correspondence: seatonba
bu.edu
Institutions: Department of Physiology and Biophysics and double daggerDepartment of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, United States
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.
Lipopolysaccharide, antigen, O-antigen, X-ray, epitope, monoclonal antibodies, Francisella tularensis, binding site, tularemia, immunochemical characterization
Structure type: oligomer
Location inside paper: abstract, fig.2a
Trivial name: epitope of the OAg, V-shaped epitope
Compound class: O-polysaccharide, O-antigen
Methods: X-ray, DNA techniques, RT-PCR
Biological activity: analysis of the antigen binding site
Biosynthesis and genetic data: genetic data
3D data: 3D data, molecular modeling
Related record ID(s): 27300, 28612, 28613, 28614
NCBI Taxonomy refs (TaxIDs): 263Reference(s) to other database(s): GTC:G59392BO
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