The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites
| العنوان: | The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites |
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| المؤلفون: | Mauld M Lamarque, Julien Papoin, Alan W. Thomas, Magali Roques, Graham Ga Bentley, Martin J. Boulanger, Juliette Morlon-Guyot, Brigitte Vulliez-Le Normand, Stanislas Tomavo, Jean-François Dubremetz, Bart Bw Faber, Clemens Ch Kocken, Maryse Lebrun, Sylvain Fauquenoy, Sébastien Besteiro |
| المصدر: | PLoS Pathogens, Vol 7, Iss 2, p e1001276 (2011) P L o S Pathogens, 7 (2 PLoS Pathogens |
| بيانات النشر: | Public Library of Science (PLoS), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Models, Molecular, Parasites -- genetics -- metabolism -- physiology, Membrane Proteins -- genetics -- metabolism -- physiology, Protozoan Proteins, Connexins, Chlorocebus aethiops, Microbiology/Parasitology, Integral membrane protein, lcsh:QH301-705.5, Cells, Cultured, Conserved Sequence, Protein Binding -- genetics, Host cell membrane, biology, Connexins -- metabolism, Sciences bio-médicales et agricoles, Cell biology, Antigens, Protozoan -- chemistry -- genetics -- metabolism, Infectious Diseases, Rhoptry neck, Microbiology/Cellular Microbiology and Pathogenesis, Toxoplasma, Research Article, Infectious Diseases/Tropical and Travel-Associated Diseases, Protein Binding, lcsh:Immunologic diseases. Allergy, Plasmodium falciparum -- genetics -- metabolism -- physiology, Plasmodium falciparum, Immunology, Antigens, Protozoan, Models, Biological, Microbiology, Host-Parasite Interactions, Cercopithecus aethiops, Apicomplexa, Virology, parasitic diseases, Genetics, Animals, Humans, Parasites, Protein Interaction Domains and Motifs, Protozoan Proteins -- chemistry -- genetics -- metabolism, Secretion, Toxoplasma -- genetics -- metabolism -- physiology, Apical membrane antigen 1, Protein Interaction Domains and Motifs -- genetics, Vero Cells, Molecular Biology, Host-Parasite Interactions -- genetics -- physiology, Rhoptry, Infectious Diseases/Protozoal Infections, Membrane Proteins, Virus Internalization, biology.organism_classification, Apicomplexa -- genetics -- metabolism -- physiology, Membrane protein, lcsh:Biology (General), Parasitology, lcsh:RC581-607 |
| الوصف: | 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. Author Summary Apicomplexa parasites are obligate intracellular pathogens causing severe diseases such as the deadly malaria or toxoplasmosis. Host cell invasion by these parasites involves the formation of a structure between the apex of the parasite and the host cell membrane called the moving junction (MJ), which is built upon collaboration between secretory organelles from the parasite that insert microneme protein AMA1 in the parasite plasma membrane and a complex of four rhoptry neck (RON2/4/5/8) proteins at the host cell plasma membrane. We have now identified a strong interaction between AMA1 and a C-terminal region of RON2, which is crucial for invasion. In spite of sequence variations in both proteins orthologs from distinct Apicomplexa, we could show that this interaction is functionally conserved and equally important for the invasive process by Toxoplasma gondii and Plasmodium falciparum. These findings open the way for therapeutic approaches that could interfere with key functions of parasitic MJ. |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe912dcfe19edb9880bed3876a3b7ad7Test http://europepmc.org/articles/PMC3037350?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fe912dcfe19edb9880bed3876a3b7ad7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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