幽门螺杆菌 Cagβ ATP 酶的 CagZ 调节机制。
Mechanism of regulation of the Helicobacter pylori Cagβ ATPase by CagZ.
机构信息
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Fujian Key Laboratory of Developmental and Neural Biology, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, Fujian, China.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
出版信息
Nat Commun. 2023 Jan 30;14(1):479. doi: 10.1038/s41467-023-36218-4.
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.
幽门螺杆菌（H. pylori）的 Cag 型 IV 型分泌系统（Cag T4SS）将 CagA 效应子运送到胃上皮细胞对于发病机制至关重要。CagA 通过 Cagβ ATP 酶被招募到 Cag T4SS。CagZ 是 H. pylori 中一种独特的蛋白质，调节 Cagβ介导的 CagA 转运，但潜在的机制尚不清楚。在这里，我们报告了 Cagβ胞质区域的晶体结构，显示出典型的环形六聚体组装。环的中央通道很窄，表明 CagA 必须展开才能通过通道运输。我们的 CagZ 与 Cagβ 的全α结构域（AAD）复合物的结构表明，CagZ 采用整体 U 形结构，并紧密包围 Cagβ。这种 CagZ 的结合模式与形成 Cagβ 六聚体（对 ATP 酶活性至关重要）不兼容。因此，CagZ 通过将 Cagβ 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模型来解释 CagA 通过 Cagβ 的运输。
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