Bryant Owain J, Fraser Gillian M
Department of Pathology, University of Cambridge, UK.
FEBS J. 2022 May;289(9):2628-2641. doi: 10.1111/febs.16294. Epub 2021 Dec 4.
Type III Secretion Systems (T3SS) transport proteins from the bacterial cytosol for assembly into cell surface nanomachines or direct delivery into target eukaryotic cells. At the core of the flagellar T3SS, the FlhAB-FliPQR export gate regulates protein entry into the export channel whilst maintaining the integrity of the cell membrane. Here, we identify critical residues in the export gate FliR plug that stabilise the closed conformation, preserving the membrane permeability barrier, and we show that the gate opens and closes in response to export substrate availability. Our data indicate that FlhAB-FliPQR gate opening, which is triggered by substrate export signals, is energised by FlhA in a proton motive force-dependent manner. We present evidence that the export substrate and the FliJ stalk of the flagellar ATPase provide mechanistically distinct, non-redundant gate-activating signals that are critical for efficient export.
III型分泌系统（T3SS）将细菌胞质溶胶中的蛋白质转运出来，用于组装成细胞表面纳米机器或直接递送至靶真核细胞中。在鞭毛T3SS的核心部位，FlhAB - FliPQR输出门调节蛋白质进入输出通道，同时维持细胞膜的完整性。在此，我们鉴定出输出门FliR塞中的关键残基，这些残基稳定关闭构象，维持膜通透性屏障，并且我们表明该门会根据输出底物的可用性打开和关闭。我们的数据表明，由底物输出信号触发的FlhAB - FliPQR门的打开，由FlhA以质子动力势依赖的方式提供能量。我们提供的证据表明，输出底物和鞭毛ATP酶的FliJ柄提供了机制上不同的、非冗余的门激活信号，这些信号对于高效输出至关重要。
