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Structure of the immunodominant surface antigen from the Toxoplasma gondii SRS superfamily

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Abstract

Toxoplasma gondii is a persistent protozoan parasite capable of infecting almost any warm-blooded vertebrate. The surface of Toxoplasma is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked proteins (SRSs), of which SAG1 is the prototypic member. SRS proteins mediate attachment to host cells and interface with the host immune response to regulate the virulence of the parasite. The 1.7 Å structure of the immunodominant SAG1 antigen reveals a homodimeric configuration in which the dimeric interface is mediated by an extended β-sheet that forms a deep groove lined with positively charged amino acids. This basic groove seems to be conserved among SRS proteins and potentially serves as a sulfated proteoglycan-binding site on target cell surfaces, thus rationalizing the promiscuous attachment properties of Toxoplasma to a broad range of host cell types.

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Figure 1: Three-dimensional structure of SAG1.
Figure 2: Dimeric interface between the D1 domains.
Figure 3: Sequence alignment of the SRS superfamily.
Figure 4: Structural mapping of the known polymorphisms of

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Acknowledgements

The authors gratefully acknowledge M. Martick, D. Chow and D. Alexander for their assistance, G. McDermott for help with MAD data collection and L. Kasper for helpful discussions. This work was funded by the NIH (K.C.G. and J.C.B.), Rita Allen Foundation (K.C.G.), American Heart Association (K.C.G.), RWJ-PRI (K.C.G.) and the California County of Alameda District Attorney's Office (J.C.B.).

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Authors and Affiliations

  1. Department of Microbiology and Immunology Fairchild Building, Fairchild Building, 299 Campus Drive, Stanford University School of Medicine, Stanford, 94305-5124, Cailfornia, USA

    Xiao-lin He, Michael E. Grigg, John C. Boothroyd & K. Christopher Garcia

  2. Department of Structural Biology, Fairchild Building, 299 Campus Drive, Stanford University School of Medicine, Stanford, 94305-5124, Cailfornia, USA

    Xiao-lin He & K. Christopher Garcia

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  1. Xiao-lin He
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  2. Michael E. Grigg
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Correspondence to K. Christopher Garcia.

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He, Xl., Grigg, M., Boothroyd, J. et al. Structure of the immunodominant surface antigen from the Toxoplasma gondii SRS superfamily. Nat Struct Mol Biol 9, 606–611 (2002). https://doi.org/10.1038/nsb819

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