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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion
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Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion

机译：疟原虫裂殖子蛋白RON2和AMA1的结合触发对入侵的承诺

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摘要

The commitment of Plasmodium 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 para-sitophorous 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 Plasmodium merozoites to RBC invasion and point to RON2 as a potential vaccine candidate.
机译：裂殖子裂殖子侵入红细胞（RBC）的承诺的特征是裂殖子与RBC之间形成连接，并协同诱导了副-平滑液泡。尽管它的重要性，对寄生虫对入侵的承诺所基于的分子事件仍未得到很好的理解。在这里，我们表明已知对入侵至关重要的两个寄生蛋白RON2和AMA1的相互作用对于触发结形成至关重要。使用结合在AMA1的疏水口袋附近和突变在口袋中的AMA1的抗体（Abs），我们确定了RON1在AMA1上的结合位点。 AMA1囊袋特异的Abs阻断了结的形成和寄生虫空泡的诱导。我们还确定了RON2肽中的关键残基（先前显示为结合AMA1），这是与AMA1口袋结合所需的关键残基，即两个保守的二硫键连接的半胱氨酸。 RON2肽阻断了结的形成，但与AMA1特异性抗体不同，它没有阻断寄生虫的液泡的形成，这表明接头和寄生虫的液泡的形成是入侵过程中分子上不同的步骤。总体而言，这些结果确定了RON2与AMA1疏水口袋的结合，这是使疟原虫裂殖子参与RBC入侵的步骤，并指出RON2是潜在的候选疫苗。

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    Prakash Srinivasan; Wandy L. Beatty; Ababacar Diouf; Raul Herrera; Xavier Ambroggio; J. Kathleen Moch; Jessica S. Tyler; David L. Narum; Susan K. Pierce; John C. Boothroyd; J. David Haynes; Louis H. Miller;

  • 作者单位

    Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;

    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63130;

    Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;

    Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;

    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;

    Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305;

    Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305;

    Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910;

    Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    ama1-ron2; malaria; moving junction;

    机译：ama1-ron2;疟疾;移动结;

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