Variant surface antigens of malaria parasites: functional and evolutionary insights from comparative gene family classification and analysis.
Variant surface antigens of malaria parasites: functional and evolutionary insights from comparative gene family classification and analysis.
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DOI：
10.1186/1471-2164-14-427
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发表时间：
2013-06-27
期刊：
影响因子：
4.4
通讯作者：
Chen N
中科院分区：
文献类型：
--
作者：
Frech C;Chen N
疟原虫是疟疾的病原体，在细胞表面表达多种不同的抗原。变异型表面抗原(VSA)通常被组织成大的亚端粒基因家族，在毒力和免疫逃避中发挥关键作用。VSA功能和进化的许多重要方面仍然不清楚，阻碍了我们对毒力机制和疫苗开发的了解。为了进一步了解VSA的功能和进化，我们对7种疟原虫的已知VSA基因家族进行了比较分类和研究。我们在最大的疟原虫基因家族PIR中确定了一组超保守的同源基因，它们应该被认为是实验功能表征和疫苗开发的高优先级靶标。此外，我们预测在红细胞表面表达的PYST-A蛋白中有一个脂结合结构域，这表明这个第二大啮齿动物寄生虫基因家族在宿主胆固醇挽救中发挥了作用。此外，研究还发现PfMC-2TM蛋白携带一个新的功能结构域MC-TYR，该结构域在其他恶性疟原虫基因家族和啮齿动物寄生虫中都是保守的。最后，我们提出了新的确凿证据，证明主要的疟原虫VSA基因PfEMP1、SICAvar和Surfin在进化上是通过一个模块化的、结构保守的胞内区相互联系的。我们对疟原虫VSA基因家族的比较分析揭示了重要的功能和进化见解，现在可以作为进一步实验研究的起点。
Plasmodium parasites, the causative agents of malaria, express many variant antigens on cell surfaces. Variant surface antigens (VSAs) are typically organized into large subtelomeric gene families that play critical roles in virulence and immune evasion. Many important aspects of VSA function and evolution remain obscure, impeding our understanding of virulence mechanisms and vaccine development. To gain further insights into VSA function and evolution, we comparatively classified and examined known VSA gene families across seven Plasmodium species. We identified a set of ultra-conserved orthologs within the largest Plasmodium gene family pir, which should be considered as high-priority targets for experimental functional characterization and vaccine development. Furthermore, we predict a lipid-binding domain in erythrocyte surface-expressed PYST-A proteins, suggesting a role of this second largest rodent parasite gene family in host cholesterol salvage. Additionally, it was found that PfMC-2TM proteins carry a novel and putative functional domain named MC-TYR, which is conserved in other P. falciparum gene families and rodent parasites. Finally, we present new conclusive evidence that the major Plasmodium VSAs PfEMP1, SICAvar, and SURFIN are evolutionarily linked through a modular and structurally conserved intracellular domain. Our comparative analysis of Plasmodium VSA gene families revealed important functional and evolutionary insights, which can now serve as starting points for further experimental studies.
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影响因子：
14.9
作者：
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影响因子：
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Fraser-Liggett, Claire M.
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作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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