The Vibrio parahaemolyticus T3SS effector VopQ targets host-cell V-ATPase, resulting in blockage of autophagic flux and neutralization of acidic compartments. Here, we report the cryo-EM structure of VopQ bound to the Vo subcomplex of the V-ATPase. VopQ inserts into membranes and forms an unconventional pore while binding directly to subunit c of the V-ATPase membrane-embedded subcomplex Vo. We show that VopQ arrests yeast growth in vivo by targeting the immature Vo subcomplex in the endoplasmic reticulum (ER), thus providing insight into the observation that VopQ kills cells in the absence of a functional V-ATPase. VopQ is a bacterial effector that has been discovered to inhibit a host-membrane megadalton complex by coincidentally binding its target, inserting into a membrane and disrupting membrane potential. Collectively, our results reveal a mechanism by which bacterial effectors modulate host cell biology and provide an invaluable tool for future studies on V-ATPase-mediated membrane fusion and autophagy.

中文翻译：

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冷冻电镜揭示了 VopQ 弧菌对 V-ATP 酶的独特抑制机制。

副溶血弧菌 T3SS 效应器 VopQ 以宿主细胞 V-ATP 酶为目标，导致自噬流受阻并中和酸性区室。在这里，我们报告了与 V-ATPase 的 Vo 子复合物结合的 VopQ 的冷冻电镜结构。VopQ 插入膜中并形成非常规孔，同时直接与 V-ATPase 膜嵌入亚复合物 Vo 的亚基 c 结合。我们发现，VopQ 通过靶向内质网 (ER) 中未成熟的 Vo 亚复合物来抑制体内酵母生长，从而深入了解 VopQ 在缺乏功能性 V-ATP 酶的情况下杀死细胞的观察结果。VopQ 是一种细菌效应子，被发现可以通过同时结合其靶标、插入膜并破坏膜电位来抑制宿主-膜兆道尔顿复合物。总的来说，我们的结果揭示了细菌效应子调节宿主细胞生物学的机制，并为未来研究 V-ATP 酶介导的膜融合和自噬提供了宝贵的工具。