Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion
Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion
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DOI：
10.1038/emboj.2008.269
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发表时间：
2009-02-18
期刊：
影响因子：
11.4
通讯作者：
Mogk, Axel
中科院分区：
文献类型：
--
作者：
Boenemann, Gabriele;Pietrosiuk, Aleksandra;Mogk, Axel
最近发现的 VI 型分泌系统 (T6SS) 在各种变形菌（包括人类病原体霍乱弧菌）的毒力中具有至关重要的功能。 T6SS 由包含大约 15 个开放阅读框的保守基因簇编码，介导细胞培养上清液中 Hcp 和 VgrG 蛋白的出现。在这里，我们分析了霍乱弧菌 T6SS 成员 ClpV（一种特殊的 AAA+ 蛋白）的功能。 ClpV 对于功能性 T6SS 至关重要，并通过其 N 端结构域与 VipA/VipB 复合体相互作用，该复合体由 T6SS 的两个保守且重要的成员组成。将 ClpV 底物特异性转移到参与蛋白水解的不同 AAA+ 蛋白会导致 VipA 降解，但不会降解 Hcp 或 VgrG2，这表明 VipA 而不是 Hcp/VgrG2 充当主要 ClpV 底物。引人注目的是，VipA/VipB 形成管状、齿轮状结构，通过 ClpV 的螺纹活性将其转化为小复合物。 ClpV 介导的 VipA/VipB 肾小管重塑代表了 T6S 中的关键步骤，阐明了 ATP 酶成分在蛋白质分泌中的意想不到的作用。
The recently identified type VI secretion systems (T6SS) have a crucial function in the virulence of various proteo-bacteria, including the human pathogen Vibrio cholerae. T6SS are encoded by a conserved gene cluster comprising approximately 15 open reading frames, mediating the appearance of Hcp and VgrG proteins in cell culture supernatants. Here, we analysed the function of the V. cholerae T6SS member ClpV, a specialized AAA+ protein. ClpV is crucial for a functional T6SS and interacts through its N-terminal domain with the VipA/VipB complex that is composed of two conserved and essential members of T6SS. Transferring ClpV substrate specificity to a distinct AAA+ protein involved in proteolysis caused degradation of VipA but not Hcp or VgrG2, suggesting that VipA rather than Hcp/VgrG2 functions as a primary ClpV substrate. Strikingly, VipA/VipB form tubular, cogwheel-like structures that are converted by a threading activity of ClpV into small complexes. ClpV-mediated remodelling of VipA/VipB tubules represents a crucial step in T6S, illuminating an unexpected role of an ATPase component in protein secretion.