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The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites.

Lamarque M, Besteiro S, Papoin J, Roques M, Vulliez-Le Normand B, Morlon-Guyot J, Dubremetz JF, Fauquenoy S, Tomavo S, Faber BW, Kocken CH, Thomas AW, Boulanger MJ, Bentley GA, Lebrun M - PLoS Pathog. (2011)

Bottom Line: AMA1, a protein secreted from micronemes and associated with the parasite surface during invasion, has been shown in vitro to bind the MJ complex through a direct association with RON2.Our studies were performed both in Toxoplasma gondii and Plasmodium falciparum and although AMA1 and RON2 proteins have diverged between Apicomplexa species, we show an intra-species conservation of their interaction.This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites.

View Article: PubMed Central - PubMed

Affiliation: UMR 5235 CNRS, Université de Montpellier 2, Montpellier, France.

ABSTRACT
Obligate intracellular Apicomplexa parasites share a unique invasion mechanism involving a tight interaction between the host cell and the parasite surfaces called the moving junction (MJ). The MJ, which is the anchoring structure for the invasion process, is formed by secretion of a macromolecular complex (RON2/4/5/8), derived from secretory organelles called rhoptries, into the host cell membrane. AMA1, a protein secreted from micronemes and associated with the parasite surface during invasion, has been shown in vitro to bind the MJ complex through a direct association with RON2. Here we show that RON2 is inserted as an integral membrane protein in the host cell and, using several interaction assays with native or recombinant proteins, we define the region that binds AMA1. Our studies were performed both in Toxoplasma gondii and Plasmodium falciparum and although AMA1 and RON2 proteins have diverged between Apicomplexa species, we show an intra-species conservation of their interaction. More importantly, invasion inhibition assays using recombinant proteins demonstrate that the RON2-AMA1 interaction is crucial for both T. gondii and P. falciparum entry into their host cells. This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites.

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Current alternative models of the RON2-AMA1 interaction at the MJ.(A) with TgRON2 C-terminal domain exposed inside the host cell; (B) with TgRON2 C-terminal domain exposed outside. TgAMA1 ectodomain was rendered from structural data ([20], (PDB ID: 2X2Z)) using Yasara view software (www.yasara.org) with molecular surface rendering. Amino acids from the hydrophobic groove region are coloured in red. No structure currently exists for TgRON2, but the protein was grossly schematized based on secondary structure predictions.
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ppat-1001276-g008: Current alternative models of the RON2-AMA1 interaction at the MJ.(A) with TgRON2 C-terminal domain exposed inside the host cell; (B) with TgRON2 C-terminal domain exposed outside. TgAMA1 ectodomain was rendered from structural data ([20], (PDB ID: 2X2Z)) using Yasara view software (www.yasara.org) with molecular surface rendering. Amino acids from the hydrophobic groove region are coloured in red. No structure currently exists for TgRON2, but the protein was grossly schematized based on secondary structure predictions.

Mentions: Overall, this has led us to precise RON2 topology at the host cell plasma membrane, as we have now identified the region of RON2 interacting with AMA1 (presumably exposed outside the host cell) and another region localized inside the host cell (Figure 8). However, the functionality of the last predicted TM domain and the disposition of the well conserved C-terminal domain are still under debate, as it could be either exposed inside, or outside the host cell (Figure 8, A and B).


The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites.

Lamarque M, Besteiro S, Papoin J, Roques M, Vulliez-Le Normand B, Morlon-Guyot J, Dubremetz JF, Fauquenoy S, Tomavo S, Faber BW, Kocken CH, Thomas AW, Boulanger MJ, Bentley GA, Lebrun M - PLoS Pathog. (2011)

Current alternative models of the RON2-AMA1 interaction at the MJ.(A) with TgRON2 C-terminal domain exposed inside the host cell; (B) with TgRON2 C-terminal domain exposed outside. TgAMA1 ectodomain was rendered from structural data ([20], (PDB ID: 2X2Z)) using Yasara view software (www.yasara.org) with molecular surface rendering. Amino acids from the hydrophobic groove region are coloured in red. No structure currently exists for TgRON2, but the protein was grossly schematized based on secondary structure predictions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037350&req=5

ppat-1001276-g008: Current alternative models of the RON2-AMA1 interaction at the MJ.(A) with TgRON2 C-terminal domain exposed inside the host cell; (B) with TgRON2 C-terminal domain exposed outside. TgAMA1 ectodomain was rendered from structural data ([20], (PDB ID: 2X2Z)) using Yasara view software (www.yasara.org) with molecular surface rendering. Amino acids from the hydrophobic groove region are coloured in red. No structure currently exists for TgRON2, but the protein was grossly schematized based on secondary structure predictions.
Mentions: Overall, this has led us to precise RON2 topology at the host cell plasma membrane, as we have now identified the region of RON2 interacting with AMA1 (presumably exposed outside the host cell) and another region localized inside the host cell (Figure 8). However, the functionality of the last predicted TM domain and the disposition of the well conserved C-terminal domain are still under debate, as it could be either exposed inside, or outside the host cell (Figure 8, A and B).

Bottom Line: AMA1, a protein secreted from micronemes and associated with the parasite surface during invasion, has been shown in vitro to bind the MJ complex through a direct association with RON2.Our studies were performed both in Toxoplasma gondii and Plasmodium falciparum and although AMA1 and RON2 proteins have diverged between Apicomplexa species, we show an intra-species conservation of their interaction.This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites.

View Article: PubMed Central - PubMed

Affiliation: UMR 5235 CNRS, Université de Montpellier 2, Montpellier, France.

ABSTRACT
Obligate intracellular Apicomplexa parasites share a unique invasion mechanism involving a tight interaction between the host cell and the parasite surfaces called the moving junction (MJ). The MJ, which is the anchoring structure for the invasion process, is formed by secretion of a macromolecular complex (RON2/4/5/8), derived from secretory organelles called rhoptries, into the host cell membrane. AMA1, a protein secreted from micronemes and associated with the parasite surface during invasion, has been shown in vitro to bind the MJ complex through a direct association with RON2. Here we show that RON2 is inserted as an integral membrane protein in the host cell and, using several interaction assays with native or recombinant proteins, we define the region that binds AMA1. Our studies were performed both in Toxoplasma gondii and Plasmodium falciparum and although AMA1 and RON2 proteins have diverged between Apicomplexa species, we show an intra-species conservation of their interaction. More importantly, invasion inhibition assays using recombinant proteins demonstrate that the RON2-AMA1 interaction is crucial for both T. gondii and P. falciparum entry into their host cells. This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites.

Show MeSH