Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin
Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin
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DOI：
10.1073/pnas.0706532104
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发表时间：
2007-09-25
影响因子：
11.1
通讯作者：
Mekalanos, John J.
中科院分区：
文献类型：
--
作者：
Pukatzki, Stefan;Ma, Amy T.;Mekalanos, John J.
编码VI型分泌系统(T6SS)的基因广泛存在于致病性革兰氏阴性菌中。在霍乱弧菌中，已发现T6SS在细胞外分泌三种相关蛋白：VgrG-1、VgrG-2和VgrG-3。在体外，VgrG-1可以共价交联肌动蛋白，这一活性被用来证明霍乱弧菌可以通过T6SS依赖的机制将VgrG-1转运到巨噬细胞中。蛋白质结构搜索算法预测，VgrG相关蛋白质很可能组装成一个三聚体复合体，类似于构成大肠杆菌噬菌体T4基板的尾部尖峰的两个三聚体蛋白gp27和gp5形成的复合体。VgrG-1被证明与自身、VgrG-2和VgrG-3相互作用，表明这样的复合体确实形成了。由于噬菌体尾钉蛋白复合体既是一个穿膜结构，又是DNA进入噬菌体感染细胞的管道，我们认为T6SS装置的VgrG组件可能组装一个类似于噬菌体尾钉的“细胞穿透装置”，通过靶宿主细胞膜运送效应蛋白结构域。
Genes encoding type VI secretion systems (T6SS) are widely distributed in pathogenic Gram-negative bacterial species. In Vibrio cholerae, T6SS have been found to secrete three related proteins extracellularly, VgrG-1, VgrG-2, and VgrG-3. VgrG-1 can covalently cross-link actin in vitro, and this activity was used to demonstrate that V. cholerae can translocate VgrG-1 into macrophages by a T6SS-dependent mechanism. Protein structure search algorithms predict that VgrG-related proteins likely assemble into a trimeric complex that is analogous to that formed by the two trimeric proteins gp27 and gp5 that make up the baseplate "tail spike" of Escherichia coli bacteriophage T4. VgrG-1 was shown to interact with itself, VgrG-2, and VgrG-3, suggesting that such a complex does form. Because the phage tail spike protein complex acts as a membrane-penetrating structure as well as a conduit for the passage of DNA into phage-infected cells, we propose that the VgrG components of the T6SS apparatus may assemble a "cellpuncturing device" analogous to phage tail spikes to deliver effector protein domains through membranes of target host cells.