A type VI secretion system effector delivery mechanism dependent on PAAR and a chaperone-co-chaperone complex
A type VI secretion system effector delivery mechanism dependent on PAAR and a chaperone-co-chaperone complex
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DOI：
10.1038/s41564-018-0144-4
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发表时间：
2018-05-01
影响因子：
28.3
通讯作者：
Dong, Tao G.
中科院分区：
文献类型：
--
作者：
Burkinshaw, Brianne J.;Liang, Xiaoye;Dong, Tao G.
VI型分泌系统（T6SS）被许多革兰氏阴性菌用作调节邻近细菌和真核细胞的分子武器，从而影响多物种环境下群落结构的动态。T6SS将其内针Hcp管、由VgrG和PAAR组成的锐尖复合物以及毒性效应器注射到邻近细胞中。它的功能在很大程度上取决于它所传递的效应器的活动。已经描述了六种效应递送机制：两种由内管介导，另一种由VgrG和PAAR尖端复合物介导。在这里，我们报告了一种额外的效应递送机制，它依赖于与伴侣复合物和PAAR蛋白作为载体的相互作用。铜绿假单胞菌PAO1含有tox - ase-5结构域的效应物TseT直接与PAAR4和伴侣蛋白TecT相互作用递送，并与免疫蛋白TsiT相互作用保护其免受毒性影响。TecT与其协同伴侣co-TecT形成复合物，该复合物被PAAR4的羧基末端尾部破坏。此外，我们描述了一个复杂的，多层次的竞争过程，决定了效应贩运。PAAR递送为工程货物蛋白转运提供了额外的工具。
The type VI secretion system (T6SS) is used by many Gram-negative bacteria as a molecular weapon to modulate neighbouring bacterial and eukaryotic cells, thereby affecting the dynamics of community structure in multiple species environments. The T6SS injects its inner-needle Hcp tube, the sharpening tip complex consisting of VgrG and PAAR, and toxic effectors into neighbouring cells. Its functions are largely determined by the activities of its delivered effectors. Six mechanisms of effector delivery have been described: two mediated by the inner tube and the others mediated by the VgrG and PAAR tip complex. Here, we report an additional effector delivery mechanism that relies on interaction with a chaperone complex and a PAAR protein as a carrier. The Pseudomonas aeruginosa PAO1 TOX-REase-5 domain-containing effector TseT directly interacts with PAAR4 and the chaperone TecT for delivery, and an immunity protein, TsiT, for protection from its toxicity. TecT forms a complex with its co-chaperone, co-TecT, which is disrupted by the carboxy-terminal tail of PAAR4. In addition, we delineate a complex, multilayered competitive process that dictates effector trafficking. PAAR delivery provides an additional tool for engineering cargo protein translocation.