Binding of<i>Plasmodium</i>merozoite proteins RON2 and AMA1 triggers commitment to invasion
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- Prakash Srinivasan
- Laboratory of Malaria and Vector Research,
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- Wandy L. Beatty
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63130;
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- Ababacar Diouf
- Laboratory of Malaria and Vector Research,
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- Raul Herrera
- Laboratory of Malaria Immunology and Vaccinology, and
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- Xavier Ambroggio
- Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
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- J. Kathleen Moch
- Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and
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- Jessica S. Tyler
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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- David L. Narum
- Laboratory of Malaria Immunology and Vaccinology, and
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- Susan K. Pierce
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
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- John C. Boothroyd
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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- J. David Haynes
- Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and
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- Louis H. Miller
- Laboratory of Malaria and Vector Research,
書誌事項
- 公開日
- 2011-07-25
- DOI
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- 10.1073/pnas.1110303108
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p>The commitment of<jats:italic>Plasmodium</jats:italic>merozoites to invade red blood cells (RBCs) is marked by the formation of a junction between the merozoite and the RBC and the coordinated induction of the parasitophorous vacuole. Despite its importance, the molecular events underlying the parasite’s commitment to invasion are not well understood. Here we show that the interaction of two parasite proteins, RON2 and AMA1, known to be critical for invasion, is essential to trigger junction formation. Using antibodies (Abs) that bind near the hydrophobic pocket of AMA1 and AMA1 mutated in the pocket, we identified RON2’s binding site on AMA1. Abs specific for the AMA1 pocket blocked junction formation and the induction of the parasitophorous vacuole. We also identified the critical residues in the RON2 peptide (previously shown to bind AMA1) that are required for binding to the AMA1 pocket, namely, two conserved, disulfide-linked cysteines. The RON2 peptide blocked junction formation but, unlike the AMA1-specific Ab, did not block formation of the parasitophorous vacuole, indicating that formation of the junction and parasitophorous vacuole are molecularly distinct steps in the invasion process. Collectively, these results identify the binding of RON2 to the hydrophobic pocket of AMA1 as the step that commits<jats:italic>Plasmodium</jats:italic>merozoites to RBC invasion and point to RON2 as a potential vaccine candidate.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 108 (32), 13275-13280, 2011-07-25
Proceedings of the National Academy of Sciences