Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences
Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences
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DOI：
10.1111/mmi.12928
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发表时间：
2015-04-01
影响因子：
3.6
通讯作者：
Vogel, Joseph P.
中科院分区：
文献类型：
--
作者：
Jeong, Kwang Cheol;Sutherland, Molly C.;Vogel, Joseph P.
嗜肺军团菌Dot/Icm T4SS 将大约 300 个效应蛋白注入宿主细胞。已提出 Dot/Icm 底物包含羧基末端信号序列，该序列对于输出是必要且充分的，尽管仅这些蛋白质的一小部分已证明这两种特征。在这项研究中，我们发现底物 SidJ 的输出是由双信号序列介导的，其中包括传统的 C 端结构域和新颖的内部基序。 C 端信号序列促进 SidJ 在感染早期点分泌到宿主细胞中，而内部信号序列则介导后期时间点的分泌。有趣的是，只有内部信号序列对于补充 sidJ 突变体的细胞内生长缺陷是必需的。尽管这是 Dot/Icm 底物由内部信号序列分泌的第一个报告，但许多其他底物可以以类似的方式导出。此外，SidJ 的有效易位依赖于类伴侣 IV 型接头 IcmS/IcmW。阐明了与两个信号序列不同的五个 IcmS/IcmW 结合域，有趣的是，只有内部信号序列介导的分泌才需要 IcmS/IcmW。因此，军团菌采用多种复杂的分子机制来调节 SidJ 的输出。
The Legionella pneumophilaDot/Icm T4SS injects approximate to 300 protein effector proteins into host cells. Dot/Icm substrates have been proposed to contain a carboxy-terminal signal sequence that is necessary and sufficient for export, although both traits have been demonstrated for only a small fraction of these proteins. In this study, we discovered that export of the substrate SidJ is mediated by dual signal sequences that include a conventional C-terminal domain and a novel internal motif. The C-terminal signal sequence facilitates secretion of SidJ into host cells at early points of infection, whereas the internal signal sequence mediates secretion at later time points. Interestingly, only the internal signal sequence is necessary for complementation of the intracellular growth defect of a sidJ mutant. Although this is the first report of a Dot/Icm substrate being secreted by an internal signal sequence, many other substrates may be exported in a similar manner. In addition, efficient translocation of SidJ is dependent on the chaperone-like type IV adaptors IcmS/IcmW. Five IcmS/IcmW binding domains that are distinct from both signal sequences were elucidated and, interestingly, only secretion mediated by the internal signal sequence requires IcmS/IcmW. Thus, Legionella employs multiple sophisticated molecular mechanisms to regulate the export of SidJ.