Toxoplasma gondii Sporozoites Invade Host Cells Using Two Novel Paralogues of RON2 and AMA1

Anna Poukchanski, Heather Fritz, Michelle L. Tonkin, Moritz Treeck, Martin J. Boulanger, John C. Boothroyd

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Toxoplasma gondii is an obligate intracellular parasite of the phylum Apicomplexa. The interaction of two well-studied proteins, Apical Membrane Antigen 1 (AMA1) and Rhoptry Neck protein 2 (RON2), has been shown to be critical for invasion by the asexual tachyzoite stage. Recently, two paralogues of these proteins, dubbed sporoAMA1 and sporoRON2 (or RON2L2), respectively, have been identified but not further characterized in proteomic and transcriptomic analyses of Toxoplasma sporozoites. Here, we show that sporoAMA1 and sporoRON2 localize to the apical region of sporozoites and that, in vitro, they interact specifically and exclusively, with no detectable interaction of sporoAMA1 with generic RON2 or sporoRON2 with generic AMA1. Structural studies of the interacting domains of sporoRON2 and sporoAMA1 indicate a novel pairing that is similar in overall form but distinct in detail from the previously described interaction of the generic pairing. Most notably, binding of sporoRON2 domain 3 to domains I/II of sporoAMA1 results in major alterations in the latter protein at the site of binding and allosterically in the membrane-proximal domain III of sporoAMA1 suggesting a possible role in signaling. Lastly, pretreatment of sporozoites with domain 3 of sporoRON2 substantially impedes their invasion into host cells while having no effect on tachyzoites, and vice versa for domain 3 of generic RON2 (which inhibits tachyzoite but not sporozoite invasion). These data indicate that sporozoites and tachyzoites each use a distinct pair of paralogous AMA1 and RON2 proteins for invasion into host cells, possibly due to the very different environment in which they each must function.

Original languageEnglish (US)
Article numbere70637
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 5 2013

Fingerprint

Sporozoites
sporozoites
Toxoplasma
Toxoplasma gondii
neck
Neck
antigens
Membranes
Antigens
tachyzoites
Proteins
proteins
cells
Apicomplexa
Proteomics
Membrane Proteins
Parasites
Binding Sites
rhoptry
transcriptomics

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Poukchanski, A., Fritz, H., Tonkin, M. L., Treeck, M., Boulanger, M. J., & Boothroyd, J. C. (2013). Toxoplasma gondii Sporozoites Invade Host Cells Using Two Novel Paralogues of RON2 and AMA1. PLoS One, 8(8), [e70637]. https://doi.org/10.1371/journal.pone.0070637

Toxoplasma gondii Sporozoites Invade Host Cells Using Two Novel Paralogues of RON2 and AMA1. / Poukchanski, Anna; Fritz, Heather; Tonkin, Michelle L.; Treeck, Moritz; Boulanger, Martin J.; Boothroyd, John C.

In: PLoS One, Vol. 8, No. 8, e70637, 05.08.2013.

Research output: Contribution to journalArticle

Poukchanski, A, Fritz, H, Tonkin, ML, Treeck, M, Boulanger, MJ & Boothroyd, JC 2013, 'Toxoplasma gondii Sporozoites Invade Host Cells Using Two Novel Paralogues of RON2 and AMA1', PLoS One, vol. 8, no. 8, e70637. https://doi.org/10.1371/journal.pone.0070637
Poukchanski, Anna ; Fritz, Heather ; Tonkin, Michelle L. ; Treeck, Moritz ; Boulanger, Martin J. ; Boothroyd, John C. / Toxoplasma gondii Sporozoites Invade Host Cells Using Two Novel Paralogues of RON2 and AMA1. In: PLoS One. 2013 ; Vol. 8, No. 8.
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