Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite.
Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite.
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DOI：
10.1073/pnas.2016775117
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发表时间：
2020-12-15
影响因子：
11.1
通讯作者：
Higgins MK
中科院分区：
文献类型：
--
作者：
Harrison TE;Reid AJ;Cunningham D;Langhorne J;Higgins MK
引起疟疾的疟原虫寄生虫在受感染宿主的血细胞内复制。这些寄生虫将少量蛋白质发送到受感染的血细胞表面，使它们能够结合宿主分子，但也有被宿主免疫系统检测到的风险。这些蛋白质已经多样化成大家族，使寄生虫能够通过使用抗原变异来避免检测。这些家族中最普遍的是疟原虫散布重复（PIR）蛋白家族。在这里，我们提出了一个PIR蛋白的结构，揭示了其胞外域的架构，并显示它是如何多样化的。最后，我们使用结构指导的方法来了解哪些小变异表面抗原家族是PIR，并了解它们在疟疾寄生虫中的进化。疟疾的致命症状发生在疟原虫寄生虫在血细胞内复制时。几种变异表面蛋白家族的成员在感染的血细胞表面上表达。其中，最大和最普遍的是疟原虫散布重复（PIR）蛋白，在一些基因组中有超过1,000种变体。它们的功能是神秘的，但在小鼠疟疾模型中，pir基因表达的差异与急性或慢性感染有关。PIR超家族的成员，以及该家族是否包括恶性疟原虫变体表面蛋白，如RIFIN和STEVORs，是有争议的。在这里，我们揭示了结构的PIR从疟原虫夏氏疟原虫的胞外结构域。我们使用结构指导的序列分析和分子建模，以表明这种折叠是发现跨PIR蛋白从小鼠和人类感染的疟疾寄生虫。此外，我们表明，RIFIN和STEVOR不是PIR。这项研究提供了一个结构指导的定义的PIR和分子框架，以了解他们的演变。
The Plasmodium parasites that cause malaria replicate within blood cells of an infected host. These parasites send a small number of proteins to infected blood cell surfaces, allowing them to bind host molecules but also risking their detection by the host immune system. These proteins have diversified into large families, allowing the parasite to avoid detection by using antigenic variation. The most ubiquitous of these families is the Plasmodium-interspersed repeat (PIR) protein family. Here we present the structure of a PIR protein, revealing the architecture of its ectodomain and showing how it has diversified. Finally, we use structure-guided methods to understand which small variant surface antigen families are PIRs and to understand their evolution across malaria parasites. The deadly symptoms of malaria occur as Plasmodium parasites replicate within blood cells. Members of several variant surface protein families are expressed on infected blood cell surfaces. Of these, the largest and most ubiquitous are the Plasmodium-interspersed repeat (PIR) proteins, with more than 1,000 variants in some genomes. Their functions are mysterious, but differential pir gene expression associates with acute or chronic infection in a mouse malaria model. The membership of the PIR superfamily, and whether the family includes Plasmodium falciparum variant surface proteins, such as RIFINs and STEVORs, is controversial. Here we reveal the structure of the extracellular domain of a PIR from Plasmodium chabaudi. We use structure-guided sequence analysis and molecular modeling to show that this fold is found across PIR proteins from mouse- and human-infective malaria parasites. Moreover, we show that RIFINs and STEVORs are not PIRs. This study provides a structure-guided definition of the PIRs and a molecular framework to understand their evolution.
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影响因子：
6.4
作者：
Carvalho, Bruna O.;Lopes, Stefanie C. P.;Costa, Fabio T. M.
通讯作者：
Costa, Fabio T. M.
影响因子：
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作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
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作者：
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通讯作者：
Otto, Thomas D
影响因子：
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作者：
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通讯作者：
Wahlgren, Mats
影响因子：
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作者：
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通讯作者：
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