Ecosystem and Public Health, Faculty of Veterinary Medicine; Biochemistry and Molecular Biology, Cumming School of Medicine; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Nat Microbiol. 2018 May;3(5):632-640. doi: 10.1038/s41564-018-0144-4. Epub 2018 Apr 9.
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.
VI 型分泌系统（T6SS）被许多革兰氏阴性菌用作分子武器，以调节邻近的细菌和真核细胞，从而影响多种物种环境中的群落结构动态。T6SS 将其内部针状 Hcp 管、由 VgrG 和 PAAR 组成的锋利尖端复合物以及毒性效应器注入邻近细胞。其功能在很大程度上取决于其输送效应器的活性。已经描述了六种效应器输送机制：两种由内部管介导，另两种由 VgrG 和 PAAR 尖端复合物介导。在这里，我们报告了一种依赖于与伴侣复合物和 PAAR 蛋白相互作用的额外效应器输送机制。铜绿假单胞菌 PAO1 TOX-REase-5 结构域包含效应物 TseT 直接与 PAAR4 和伴侣 TecT 相互作用进行输送，并与免疫蛋白 TsiT 相互作用以防止其毒性。TecT 与共伴侣 co-TecT 形成复合物，该复合物被 PAAR4 的羧基末端尾巴破坏。此外，我们描绘了一个复杂的、多层次的竞争过程，决定了效应物的运输。PAAR 输送为工程货物蛋白易位提供了另一种工具。
