Diverse roles of TssA-like proteins in the assembly of bacterial Type VI secretion systems.

Protein translocation by the bacterial Type VI secretion system (T6SS) is driven by a rapid contraction of a sheath assembled around a tube with associated effectors. Here we show that TssA-like or TagA-like proteins with a conserved N-terminal domain and varying C-terminal domains can be grouped into at least three distinct classes based on their role in sheath assembly. The proteins of the first class increase speed and frequency of sheath assembly and form a stable dodecamer at the distal end of a polymerizing sheath. The proteins of the second class localize to the cell membrane and block sheath polymerization upon extension across the cell. This prevents excessive sheath polymerization and bending, which may result in sheath destabilization and detachment from its membrane anchor and thus result in failed secretion. The third class of these proteins localize to the baseplate and are required for initiation of sheath assembly. Our work shows that while various proteins share a conserved N-terminal domain their roles in T6SS biogenesis are fundamentally different.

细菌VI型分泌系统（Type VI secretion system, T6SS）介导的蛋白质转运，依赖于环绕携带相关效应蛋白的管道组装而成的鞘的快速收缩。本研究表明，携带保守N端结构域与可变C端结构域的类TssA蛋白及类TagA蛋白，可根据其在鞘组装过程中的功能分为至少三个不同类别。第一类蛋白可提升鞘组装的速度与频率，并在正在聚合的鞘的远端形成稳定的十二聚体。第二类蛋白定位于细胞膜，在鞘跨细胞延伸时阻断其聚合，这一过程可防止过度的鞘聚合与弯曲——后者可能导致鞘解稳定并脱离其膜锚定位点，最终引发分泌失败。第三类蛋白定位于基底板，是鞘组装起始所必需的。本研究证实，尽管各类蛋白共享保守的N端结构域，它们在T6SS生物发生过程中的功能却存在根本性差异。