Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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

Nature Structural Biology volume 9, pages 606–611 (2002)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

Accession codes

Accessions

Protein Data Bank

References

  1. Suzuki, Y., Conley, F.K. & Remington, J.S. J. Infect. Dis. 159, 790–794 (1989).

    Article  CAS  Google Scholar 

  2. Luft, B.J. & Remington, J.S. Clin. Infect. Dis. 15, 211–222 (1992).

    Article  CAS  Google Scholar 

  3. Grigg, M.E., Ganatra, J., Boothroyd, J.C. & Margolis, T.P. J. Infect. Dis. 184, 633–639 (2001).

    Article  CAS  Google Scholar 

  4. Boothroyd, J.C., Hehl, A., Knoll, L.J. & Manger, I.D. Int. J. Parasitol. 28, 3–9 (1998).

    Article  CAS  Google Scholar 

  5. Lekutis, C., Ferguson, D.J., Grigg, M.E., Camps, M. & Boothroyd, J.C. Int. J. Parasitol. 31, 1285–1292 (2001).

    Article  CAS  Google Scholar 

  6. Lekutis, C., Ferguson, D.J. & Boothroyd, J.C. Exp. Parasitol. 96, 89–96 (2000).

    Article  CAS  Google Scholar 

  7. Manger, I.D., Hehl, A.B. & Boothroyd, J.C. Infect. Immun. 66, 2237–2244 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Cross, G.A. Annu. Rev. Immunol. 8, 83–110 (1990).

    Article  CAS  Google Scholar 

  9. Jacquet, A. et al. Mol. Biochem. Parasitol. 116, 35–44 (2001).

    Article  CAS  Google Scholar 

  10. Mineo, J.R. et al. J. Immunol. 150, 3951–3964 (1993).

    CAS  PubMed  Google Scholar 

  11. Grimwood, J. & Smith, J.E. Int. J. Parasitol. 26, 169–173 (1996).

    Article  CAS  Google Scholar 

  12. Dzierszinski, F., Mortuaire, M., Cesbron-Delauw, M.F. & Tomavo, S. Mol. Microbiol. 37, 574–582 (2000).

    Article  CAS  Google Scholar 

  13. Rodriguez, C., Afchain, D., Capron, A., Dissous, C. & Santoro, F. Eur. J. Immunol. 15, 747–749 (1985).

    Article  CAS  Google Scholar 

  14. Adman, E.T. Adv. Protein Chem. 42, 145–197 (1991).

    Article  CAS  Google Scholar 

  15. Baker, E.N. J. Mol. Biol. 203, 1071–1095 (1988).

    Article  CAS  Google Scholar 

  16. Lawrence, M.C. & Colman, P.M. J. Mol. Biol. 234, 946–950 (1993).

    Article  CAS  Google Scholar 

  17. Ortega-Barria, E. & Boothroyd, J.C. J. Biol. Chem. 274, 1267–1276 (1999).

    Article  CAS  Google Scholar 

  18. Pellegrini, L. et al. Biochem. Soc. Trans. 26, 545–549 (1998).

    Article  CAS  Google Scholar 

  19. Hobbs, M.R. & Boothroyd, J.C. Mol. Biochem. Parasitol. 43, 1–16 (1990).

    Article  CAS  Google Scholar 

  20. Salmon, D. et al. EMBO J. 16, 7272–7278 (1997).

    Article  CAS  Google Scholar 

  21. Grigg, M.E., Bonnefoy, S., Hehl, A.B., Suzuki, Y. & Boothroyd, J.C. Science 294, 161–165 (2001).

    Article  CAS  Google Scholar 

  22. Hehl, A., Krieger, T. & Boothroyd, J.C. Mol. Biochem. Parasitol. 89, 271–282 (1997).

    Article  CAS  Google Scholar 

  23. Spano, F. et al. Int. J. Parasitol. 32, 121–131 (2002).

    Article  CAS  Google Scholar 

  24. Kabsch, W. J. Appl. Crystallogr. 21, 916–924 (1988).

    Article  CAS  Google Scholar 

  25. Otwinowski, Z. in Proceedings of the CCP4 Study Weekend (ed. Sawyer, L., Isaacs, N. & Bailey, S.) 56–62 (SERC Daresbury Laboratory, UK; 1993).

    Google Scholar 

  26. Brünger, A.T. et al. Acta Crystallogr. D 54, 905–921 (1998).

    Article  Google Scholar 

  27. Perrakis, A., Morris, R. & Lamzin, V.S. Nature Struct. Biol. 6, 458–463 (1999).

    Article  CAS  Google Scholar 

  28. Jones, T.A., Zou, J.Y., Cowan, S.W. & Kjeldgaard, M. Acta Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  29. Laskowski, R.A., MacArthur, M.W., Moss, D.S. & Thornton, J.M. J. Appl. Crystallogr. 26, 283–291 (1993).

    Article  CAS  Google Scholar 

  30. Sanchez, R. & Sali, A. Proteins Suppl. 1, 50–58 (1997).

  31. Kraulis, P.J. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  32. Merritt, E.A. & Bacon, D.J. Methods Enzymol. 277, 505–524 (1997).

    Article  CAS  Google Scholar 

  33. Nichols, A., Sharp, K.A. & Honig, B. Proteins 11, 281–296 (1991).

    Article  Google Scholar 

  34. Read, R.J. Acta Crystallogr. A 54, 140–149 (1986).

    Article  Google Scholar 

Download references

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.).

Author information

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

Authors
  1. Xiao-lin He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael E. Grigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John C. Boothroyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Christopher Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Christopher Garcia.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsb819

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing