Targeting of tail-anchored membrane proteins to subcellular organelles in Toxoplasma gondii.
Targeting of tail-anchored membrane proteins to subcellular organelles in Toxoplasma gondii.
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尾锚定膜蛋白靶向弓形虫的亚细胞器。
DOI：
10.1111/tra.12464
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
SullivanJr,WilliamJ
中科院分区：
文献类型：
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作者：
Padgett,LeahR;Arrizabalaga,Gustavo;SullivanJr,WilliamJ
正确的蛋白定位对于关键的细胞过程是必不可少的，包括囊泡介导的运输和蛋白质易位。尾锚定（TA）蛋白通过C末端整合到细胞器膜中，使N末端朝向细胞质。TA蛋白的定位发生在翻译后，并由C末端控制，其中包含完整的跨膜结构域（TMD）和靶向序列。TA蛋白的靶向依赖于TMD的疏水性以及侧翼氨基酸序列的长度和组成。我们以前确定了一个不寻常的同源物的延长蛋白，Elp3，在apicomplexan寄生虫弓形虫的TA蛋白靶向外线粒体膜。我们试图以这种早期分支的真核生物为模型，进一步深入了解TA蛋白及其靶向机制。我们的生物信息学分析揭示了弓形虫中59个预测的TA蛋白，其中9个基于代表性特征被选择用于后续分析。我们发现了新的TA蛋白，运输到特定的细胞器inToxoplasma，包括寄生虫内质网，内质网，高尔基体。结构域交换实验阐明了TA蛋白靶向这些特定细胞器受到TMD序列的强烈影响，包括侧翼C末端序列的电荷。
Proper protein localization is essential for critical cellular processes, including vesicle‐mediated transport and protein translocation. Tail‐anchored (TA) proteins are integrated into organellar membranes via the C‐terminus, orienting the N‐terminus towards the cytosol. Localization of TA proteins occurs posttranslationally and is governed by the C‐terminus, which contains the integral transmembrane domain (TMD) and targeting sequence. Targeting of TA proteins is dependent on the hydrophobicity of the TMD as well as the length and composition of flanking amino acid sequences. We previously identified an unusual homologue of elongator protein, Elp3, in the apicomplexan parasiteToxoplasma gondiias a TA protein targeting the outer mitochondrial membrane. We sought to gain further insight into TA proteins and their targeting mechanisms using this early‐branching eukaryote as a model. Our bioinformatics analysis uncovered 59 predicted TA proteins inToxoplasma, 9 of which were selected for follow‐up analyses based on representative features. We identified novel TA proteins that traffic to specific organelles inToxoplasma, including the parasite endoplasmic reticulum, mitochondrion, and Golgi apparatus. Domain swap experiments elucidated that targeting of TA proteins to these specific organelles was strongly influenced by the TMD sequence, including charge of the flanking C‐terminal sequence.