Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
Elife. 2020 Dec 15;9:e62816. doi: 10.7554/eLife.62816.
Type VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighboring bacteria. Many effectors harbor N-terminal ransembrane omains (TMDs) implicated in effector translocation across target cell membranes. However, the distribution of these TMD-containing effectors remains unknown. Here, we discover prePAAR, a conserved motif found in over 6000 putative TMD-containing effectors encoded predominantly by 15 genera of Proteobacteria. Based on differing numbers of TMDs, effectors group into two distinct classes that both require a member of the Eag family of T6SS chaperones for export. Co-crystal structures of class I and class II effector TMD-chaperone complexes from Typhimurium and , respectively, reveals that Eag chaperones mimic transmembrane helical packing to stabilize effector TMDs. In addition to participating in the chaperone-TMD interface, we find that prePAAR residues mediate effector-VgrG spike interactions. Taken together, our findings reveal mechanisms of chaperone-mediated stabilization and secretion of two distinct families of T6SS membrane protein effectors.
VI 型分泌系统 (T6SS) 在相邻细菌之间输送抗菌效应蛋白。许多效应器都具有 N 端跨膜结构域 (TMD)，这些结构域被认为在效应蛋白穿过靶细胞膜的过程中发挥作用。然而，这些含有 TMD 的效应器的分布尚不清楚。在这里，我们发现了 prePAAR，这是一个在超过 6000 种假定的含有 TMD 的效应器中发现的保守基序，这些效应器主要由 15 个属的 Proteobacteria 编码。根据 TMD 的数量不同，效应器分为两类，这两类都需要 T6SS 伴侣蛋白家族的 Eag 成员进行输出。来自 鼠伤寒沙门氏菌 和 的 I 类和 II 类效应器 TMD-伴侣复合物的共晶结构分别揭示了 Eag 伴侣蛋白模拟跨膜螺旋包装以稳定效应器 TMD。除了参与伴侣蛋白-TMD 界面外，我们还发现 prePAAR 残基介导效应器-VgrG 刺突相互作用。总之，我们的研究结果揭示了两种不同的 T6SS 膜蛋白效应器的伴侣蛋白介导的稳定和分泌机制。
