title: Crystal structure of the complex between the monomeric form of Toxoplasma gondii surface antigen 1 (SAG1) and a monoclonal antibody that mimics the human immune response.
abstract: Toxoplasma gondii, the intracellular parasite responsible for toxoplasmosis infects more than one-third of the world population and can be life-threatening for fetuses and immunocompromised patients. The surface protein SAG1 is an important immune target, which provides a strong immune response against the invasive tachyzoite while the other forms of the parasite, devoid of SAG1 at their surface, are multiplying. In addition to this role as a "hot spot" decoy, SAG1 is predicted to act as an adhesin during host-cell attachment through its binding to proteoglycans. To begin to understand the relationships between SAG1 epitopes and the ligand-binding site, we have solved the crystal structure of the monomeric form of T.gondii SAG1 complexed to a Fab derived from a monoclonal antibody raised against tachyzoite particles. This antibody competes strongly with human Toxoplasma-specific sera, suggesting that its epitope is part of an immunodominant region present on the surface of SAG1. The structure reveals that this conformational epitope, located within the SAG1 N-terminal domain, does not overlap with the proposed ligand-binding pocket. This study provides the first structural description of the monomeric form of SAG1, and significant insights into its dual role of adhesin and immune target during parasite infection.
authors.affiliation: Département d'Ingénierie et d'Etudes des Protéines, Centre d'Etudes de Saclay, 91191 Gif-sur-Yvette, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Graille
authors.forename: Enrico A
authors.initials: EA
authors.lastname: Stura
authors.forename: Marc
authors.initials: M
authors.lastname: Bossus
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Muller
authors.forename: Odile
authors.initials: O
authors.lastname: Letourneur
authors.forename: Nicole
authors.initials: N
authors.lastname: Battail-Poirot
authors.forename: Geneviève
authors.initials: G
authors.lastname: Sibaï
authors.forename: Marie
authors.initials: M
authors.lastname: Gauthier
authors.forename: Dominique
authors.initials: D
authors.lastname: Rolland
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Le Du
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ducancel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D016056:Immunodominant Epitopes; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D016056:Immunodominant Epitopes; D008024:Ligands; D010446:Peptide Fragments; D015800:Protozoan Proteins; C047168:SAG1 antigen, Toxoplasma