Structure and Function of the Dot/Icm T4SS
Structure and Function of the Dot/Icm T4SS
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DOI：
10.1101/2023.03.22.533729
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Przemysław Dutka;Yuxi Liu;S. Maggi;D. Ghosal;Jue Wang;S. Carter;Wei Zhao;Sukhithasri Vijayrajratnam;J. Vogel;G. Jensen
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文献类型：
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作者：
Przemysław Dutka;Yuxi Liu;S. Maggi;D. Ghosal;Jue Wang;S. Carter;Wei Zhao;Sukhithasri Vijayrajratnam;J. Vogel;G. Jensen
嗜肺军团菌Dot/Icm IV型分泌系统（T4SS）在感染期间向宿主细胞递送效应蛋白。尽管其作为潜在药物靶标具有重要意义，但我们目前对其原子结构的了解仅限于分离的亚络合物。在本研究中，我们采用亚层图平均和综合建模的方法构建了一个包含17种蛋白质成分的Dot/Icm T4SS的近乎完整的模型。我们定位并提供了包括DotI、DotJ、DotU、IcmF、IcmT和IcmX在内的六个新组件的结构和功能的见解。我们发现IcmF的细胞质n端结构域，一个形成中心空心圆柱体的关键蛋白，与DotU相互作用，提供了以前未表征的密度的见解。此外，我们的模型结合成分异质性分析，解释了细胞质atp酶DotO如何通过与膜结合的DotI/DotJ蛋白相互作用与质周复合体连接。结合原位感染数据，我们的模型为t4ss介导的分泌机制提供了新的见解。
The Legionella pneumophila Dot/Icm type IV secretion system (T4SS) delivers effector proteins into host cells during infection. Despite its significance as a potential drug target, our current understanding of its atomic structure is limited to isolated subcomplexes. In this study, we used subtomogram averaging and integrative modeling to construct a nearly-complete model of the Dot/Icm T4SS accounting for seventeen protein components. We locate and provide insights into the structure and function of six new components including DotI, DotJ, DotU, IcmF, IcmT, and IcmX. We find that the cytosolic N-terminal domain of IcmF, a key protein forming a central hollow cylinder, interacts with DotU, providing insight into previously uncharacterized density. Furthermore, our model, in combination with analyses of compositional heterogeneity, explains how the cytoplasmic ATPase DotO is connected to the periplasmic complex via interactions with membrane-bound DotI/DotJ proteins. Coupled with in situ infection data, our model offers new insights into the T4SS-mediated secretion mechanism.