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.
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.
Graille
Marc
M
Département d'Ingénierie et d'Etudes des Protéines, Centre d'Etudes de Saclay, 91191 Gif-sur-Yvette, France.
Stura
Enrico A
EA
Bossus
Marc
M
Muller
Bruno H
BH
Letourneur
Odile
O
Battail-Poirot
Nicole
N
Sibaï
Geneviève
G
Gauthier
Marie
M
Rolland
Dominique
D
Le Du
Marie-Hélène
MH
Ducancel
Frédéric
F
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*
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