Abstract：
The transport of the CagA effector into gastric epithelial cells by the Cag Type IV secretion system (Cag T4SS) of Helicobacter pylori (H. pylori) is critical for pathogenesis. CagA is recruited to Cag T4SS by the Cagβ ATPase. CagZ, a unique protein in H. pylori, regulates Cagβ-mediated CagA transport, but the underlying mechanisms remain unclear. Here we report the crystal structure of the cytosolic region of Cagβ, showing a typical ring-like hexameric assembly. The central channel of the ring is narrow, suggesting that CagA must unfold for transport through the channel. Our structure of CagZ in complex with the all-alpha domain (AAD) of Cagβ shows that CagZ adopts an overall U-shape and tightly embraces Cagβ. This binding mode of CagZ is incompatible with the formation of the Cagβ hexamer essential for the ATPase activity. CagZ therefore inhibits Cagβ by trapping it in the monomeric state. Based on these findings, we propose a refined model for the transport of CagA by Cagβ.
摘要：
通过幽门螺杆菌的CagIV型分泌系统（CagT4SS）将CagA效应子转运到胃上皮细胞中（H。pylori)是发病机制的关键。CagA通过CagβATP酶募集到CagT4SS。CagZ,幽门螺杆菌中一种独特的蛋白质，调节Cagβ介导的CagA转运，但潜在的机制仍不清楚。在这里，我们报告了Cagβ的胞浆区域的晶体结构，显示典型的环状六聚体组件。环的中央通道很窄，这表明CagA必须展开才能通过通道运输。我们与Cagβ的全α结构域（AAD）复合的CagZ结构表明，CagZ呈整体U形，并紧密包围Cagβ。CagZ的这种结合模式与ATPase活性所必需的Cagβ六聚体的形成不相容。因此,CagZ通过将其捕获在单体状态来抑制Cagβ。基于这些发现,我们提出了一个改进的CagA通过Cagβ转运的模型。
