The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner.
The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner.
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DOI：
10.1016/j.molbiopara.2016.09.004
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发表时间：
2017-01
影响因子：
1.5
通讯作者：
Dessens JT
中科院分区：
文献类型：
--
作者：
Al-Khattaf FS;Tremp AZ;El-Houderi A;Dessens JT
肺泡蛋白 IMC1a 的末端半胱氨酸基序稳定蛋白质。 IMC1a 消耗剂量依赖性地影响子孢子形态发生。子孢子大小与子孢子感染性相关。顶复门寄生虫具有由中间丝组成的独特的皮质细胞骨架结构。它的构建模块由称为肺泡蛋白的保守蛋白质家族提供。核心肺泡结构由串联重复序列组成，被认为是这些蛋白质的丝状特性的原因。肺泡蛋白的子集还具有由位于多肽末端附近的三个紧密间隔的半胱氨酸残基组成的保守基序。这些半胱氨酸基序的作用及其对肺泡蛋白功能的贡献仍然知之甚少。子孢子表达的 IMC1a 在疟原虫肺泡蛋白家族中是独特的，因为在两个末端都具有保守的半胱氨酸基序。使用转基因伯氏疟原虫寄生虫，我们在结构功能分析中表明，氨基或羧基末端半胱氨酸基序的诱变导致寄生虫中IMC1a蛋白水平显着降低，同时伴随着子孢子形状和感染性的部分丧失。我们的研究结果为肺泡蛋白功能提供了新的见解，确定了肺泡蛋白消耗对子孢子大小和感染性的剂量依赖性影响，以及末端半胱氨酸基序在维持寄生虫肺泡蛋白稳定性中的重要作用。
The terminal cysteine motifs of the alveolin IMC1a stabilise the protein. IMC1a depletion dose-dependently affects sporozoite morphogenesis. Sporozoite size correlates with sporozoite infectivity. Apicomplexan parasites possess a unique cortical cytoskeleton structure composed of intermediate filaments. Its building blocks are provided by a conserved family of proteins named alveolins. The core alveolin structure is made up of tandem repeat sequences, thought to be responsible for the filamentous properties of these proteins. A subset of alveolins also possess conserved motifs composed of three closely spaced cysteine residues situated near the ends of the polypeptides. The roles of these cysteine motifs and their contribution to alveolin function remains poorly understood. The sporozoite-expressed IMC1a is unique within the Plasmodium alveolin family in having conserved cysteine motifs at both termini. Using transgenic Plasmodium berghei parasites, we show in this structure-function analysis that mutagenesis of the amino- or carboxy-terminal cysteine motif causes marked reductions in IMC1a protein levels in the parasite, which are accompanied by partial losses of sporozoite shape and infectivity. Our findings give new insight into alveolin function, identifying a dose-dependent effect of alveolin depletion on sporozoite size and infectivity, and vital roles of the terminal cysteine motifs in maintaining alveolin stability in the parasite.