The Legionella IcmS-IcmW protein complex is important for Dot/Icm-mediated protein translocation
The Legionella IcmS-IcmW protein complex is important for Dot/Icm-mediated protein translocation
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DOI：
10.1111/j.1365-2958.2004.04435.x
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发表时间：
2005-02-01
影响因子：
3.6
通讯作者：
Roy, CR
中科院分区：
文献类型：
--
作者：
Ninio, S;Zuckman-Cholon, DM;Roy, CR
细胞内病原体嗜肺军团菌可以感染人类宿主的巨噬细胞并在其中复制。为了建立感染，军团菌需要Dot/Icm分泌系统将蛋白质底物直接注射到宿主细胞质中。底物蛋白通过Dot/Icm系统接合和移位的机制还不清楚。在这里，我们表明，两个胞质组分的点/Icm分泌机制，蛋白质IcmS和IcmW，底物易位中发挥重要作用。生化分析表明，IcmS和IcmW形成一个稳定的蛋白质复合物。在军团菌中，IcmW蛋白在不存在IcmS蛋白的情况下迅速降解。通过Dot/Icm系统易位到哺乳动物宿主细胞中的底物蛋白使用IcmW蛋白作为诱饵在酵母双杂交筛选中鉴定。已确定IcmS-IcmW复合物与这些底物相互作用，并在这些蛋白质易位到哺乳动物细胞中起重要作用。这些数据与IcmS-IcmW复合物在军团菌感染宿主细胞期间参与底物蛋白的识别和Dot/Icm依赖性移位一致。
The intracellular pathogen Legionella pneumophila can infect and replicate within macrophages of a human host. To establish infection, Legionella require the Dot/Icm secretion system to inject protein substrates directly into the host cell cytoplasm. The mechanism by which substrate proteins are engaged and translocated by the Dot/Icm system is not well understood. Here we show that two cytosolic components of the Dot/Icm secretion machinery, the proteins IcmS and IcmW, play an important role in substrate translocation. Biochemical analysis indicates that IcmS and IcmW form a stable protein complex. In Legionella, the IcmW protein is rapidly degraded in the absence of the IcmS protein. Substrate proteins translocated into mammalian host cells by the Dot/Icm system were identified using the IcmW protein as bait in a yeast two-hybrid screen. It was determined that the IcmS-IcmW complex interacts with these substrates and plays an important role in translocation of these proteins into mammalian cells. These data are consistent with the IcmS-IcmW complex being involved in the recognition and Dot/Icm-dependent translocation of substrate proteins during Legionella infection of host cells.