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High affinity interactions between red blood cell receptors and synthetic Plasmodium thrombospondin-related apical merozoite protein (PTRAMP) peptides

机译:红细胞受体与合成疟原虫血小板反应蛋白相关的根部裂殖子蛋白(PTRAMP)肽之间的高亲和力相互作用

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摘要

Plasmodium falciparum thrombospondin-related apical merozoite protein (PTRAMP) has a thrombospondin related (TSR) domain which in many proteins has been reported as a fragment involved in pathogen-host and cell-interactions. Receptor-ligand studies using eighteen non-overlapping 20-aminoacid-long synthetic peptides from this protein were carried out to determine regions involved in parasite invasion of red blood cells (RBC). Two high activity binding peptides (HABPs) were determined, 33405 (~(21)YISSNDLTSTNLKVRNNWEH~(40)) and 33413 (~(180)LEGPIQFSLGKSSGAFRINY~(199)), presenting high dissociation constants and positive cooperativity. One of the HABPs displayed a modified Plasmodium export element (PEXEL), suggesting that this protein could be involved in the merozoite cytoplasmic reticulum, para-sitophorous vacuole, red blood cell (RBC) cytosol, and probably infected RBC (iRBC) membrane transport of some other molecules and nutrients. Enzymatic treatment of RBCs increased HABP 33405 binding to them whilst it decreased HABP 33413 binding. Merozoite invasion assays revealed that HABPs have around 57% ability to inhibit new RBC invasion. Circular dichroism revealed the presence of possible α-helical elements in both HABPs structures. RBC binding interaction specificity and the presence of a PEXEL motif make these 2 HABPs good candidates for being included in further studies to develop a new multi-antigenic, multi-stage, subunit-based, chemically-synthesised, anti-malarial vaccine.
机译:恶性疟原虫血小板反应蛋白相关的根部裂殖子蛋白(PTRAMP)具有血小板反应蛋白相关的(TSR)结构域,在许多蛋白中,已报道该蛋白为涉及病原体-宿主和细胞相互作用的片段。进行了使用来自该蛋白质的18个非重叠的20个氨基酸长的合成肽进行受体-配体研究,以确定参与寄生虫侵袭红细胞(RBC)的区域。确定了两个高活性结合肽(HABP),33405(〜(21)YISSNDLTSTNLKVRNNWEH〜(40))和33413(〜(180)LEGPIQFSLGKSSGAFRINY〜(199)),具有高解离常数和正协同性。其中一个HABPs显示出修饰的疟原虫输出元件(PEXEL),表明该蛋白可能与裂殖子的胞质网,副表皮液泡,红细胞(RBC)胞质溶胶以及可能感染的RBC(iRBC)膜转运有关。其他一些分子和营养。酶处理红细胞可增加HABP 33405与之的结合,同时降低HABP 33413的结合。裂殖子侵袭试验显示HABP具有抑制新RBC侵袭的能力约57%。圆二色性表明在两个HABPs结构中都可能存在α-螺旋元素。 RBC结合相互作用的特异性和PEXEL基序的存在使这2种HABPs成为了进一步研究开发新的多抗原,多阶段,亚基,化学合成的抗疟疾疫苗的理想候选者。

著录项

  • 来源
    《Biochimie》 |2008年第5期|802-810|共9页
  • 作者单位

    Fundacion Instituto de Inmunologia de Colombia and Universidad Nacional de Colombia, Bogota, Colombia;

    Fundacion Instituto de Inmunologia de Colombia and Universidad Nacional de Colombia, Bogota, Colombia;

    Fundacion Instituto de Inmunologia de Colombia and Universidad Nacional de Colombia, Bogota, Colombia;

    Fundacion Instituto de Inmunologia de Colombia and Universidad Nacional de Colombia, Bogota, Colombia;

    Fundacion Instituto de Inmunologia de Colombia and Universidad Nacional de Colombia, Bogota, Colombia;

    Fundacion Institute de Inmunologia de Colombia, Carrera 50, No 26-00, 020304 CAN, Bogota, Colombia;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    plasmodium falciparum; PTRAMP; thrombospondin; HABP;

    机译:恶性疟原虫PTRAMP;血小板反应蛋白HABP;
  • 入库时间 2022-08-18 01:24:09

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