Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW72AZ, UK.
Int J Parasitol. 2011 Aug 15;41(10):1029-39. doi: 10.1016/j.ijpara.2011.05.007. Epub 2011 Jun 22.
The transformation of malaria ookinetes into oocysts occurs in the mosquito midgut and is a major bottleneck for parasite transmission. The secreted ookinete surface protein, circumsporozoite- and thrombospondin-related adhesive protein (TRAP)-related protein (CTRP), is essential for this transition and hence constitutes a potential target for malaria transmission blockade. CTRP is a modular multidomain protein containing six tandem von Willebrand factor A-like (A) domains and seven tandem thrombospondin type I repeat-like (TS) domains. Here we present, to our knowledge, the first structure-function analysis of CTRP using genetically modified Plasmodium berghei parasites expressing mutant versions of the ctrp gene. Our data show that the A domains of CTRP are critical for ookinete gliding motility and oocyst formation whilst, unexpectedly, its TS domains are fully redundant. These results may have important implications for the design of CTRP-based transmission blocking strategies.
疟原虫配子体转化为卵囊发生在蚊的中肠，是寄生虫传播的主要瓶颈。分泌的配子体表蛋白——环子孢子蛋白和血小板反应蛋白相关黏附蛋白（TRAP）相关蛋白（CTRP），对于这种转化至关重要，因此构成了疟疾传播阻断的潜在靶点。CTRP 是一种模块化的多结构域蛋白，包含六个串联的血管性血友病因子 A 样（A）结构域和七个串联的血小板反应蛋白 I 型重复样（TS）结构域。在这里，我们使用表达突变 ctrp 基因的遗传修饰的伯氏疟原虫寄生虫，进行了 CTRP 的首次结构-功能分析，据我们所知，这是首次分析。我们的数据表明，CTRP 的 A 结构域对于配子体的滑行运动和卵囊的形成至关重要，而令人意外的是，其 TS 结构域是完全冗余的。这些结果可能对基于 CTRP 的传播阻断策略的设计具有重要意义。
