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首页> 外文期刊>Infection and immunity >Binding Hot Spot for Invasion Inhibitory Molecules on Plasmodium falciparum Apical Membrane Antigen 1
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Binding Hot Spot for Invasion Inhibitory Molecules on Plasmodium falciparum Apical Membrane Antigen 1

机译：结合热点对恶性疟原虫顶端膜抗原1的入侵抑制分子。

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Apical membrane antigen 1 (AMA1) is expressed in schizont-stage malaria parasites and sporozoites and is thought to be involved in the invasion of host red blood cells. AMA1 is an important vaccine candidate, as immunization with this antigen induces a protective immune response in rodent and monkey models of human malaria. Additionally, anti-AMA1 polyclonal and monoclonal antibodies inhibit parasite invasion in vitro. We have isolated a 20-residue peptide (R1) from a random peptide library that binds to native AMA1 as expressed by Plasmodium falciparum parasites. Binding of R1 peptide is dependent on AMA1 having the proper conformation, is strain specific, and results in the inhibition of merozoite invasion of host erythrocytes. The solution structure of R1, as determined by nuclear magnetic resonance spectroscopy, contains two structured regions, both involving turns, but the first region, encompassing residues 5 to 10, is hydrophobic and the second, at residues 13 to 17, is more polar. Several lines of evidence reveal that R1 targets a “hot spot” on the AMA1 surface that is also recognized by other peptides and monoclonal antibodies that have previously been shown to inhibit merozoite invasion. The functional consequence of binding to this region by a variety of molecules is the inhibition of merozoite invasion into host erythrocytes. The interaction between these peptides and AMA1 may further our understanding of the molecular mechanisms of invasion by identifying critical functional regions of AMA1 and aid in the development of novel antimalarial strategies.
机译：顶膜抗原1（AMA1）在裂殖体期疟原虫和子孢子中表达，并被认为与宿主红细胞的入侵有关。 AMA1是重要的候选疫苗，因为用这种抗原免疫可在人疟疾的啮齿动物和猴子模型中诱导保护性免疫应答。此外，抗AMA1多克隆抗体和单克隆抗体在体外可抑制寄生虫入侵。我们从随机肽库中分离出20个残基的肽（R1），该肽库可与恶性疟原虫寄生虫表达的天然AMA1结合。 R1肽的结合依赖于具有适当构象的AMA1，是菌株特异性的，并导致抑制裂殖子入侵宿主红细胞。通过核磁共振波谱确定的R1的溶液结构包含两个结构化的区域，均涉及匝，但第一个包含残基5至10的区域是疏水的，第二个区域在残基13至17的极性更大。几条证据表明，R1靶向AMA1表面上的“热点”，该点也被先前已显示出抑制裂殖子入侵的其他肽和单克隆抗体识别。通过多种分子结合到该区域的功能结果是抑制裂殖子侵入宿主红细胞。这些肽与AMA1之间的相互作用可能会通过识别AMA1的关键功能区进一步帮助我们了解侵袭的分子机制，并有助于开发新的抗疟疾策略。

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