The substrate specificity switch FlhB assembles onto the export gate to regulate type three secretion
The substrate specificity switch FlhB assembles onto the export gate to regulate type three secretion
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DOI：
10.1038/s41467-020-15071-9
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发表时间：
2020-03-10
影响因子：
16.6
通讯作者：
Lea, Susan M.
中科院分区：
文献类型：
--
作者：
Kuhlen, Lucas;Johnson, Steven;Lea, Susan M.
通过3型分泌系统（T3SS）分泌蛋白质对许多细菌的运动和毒力至关重要。蛋白质通过包含三种蛋白质（鞭毛中的FliPQR，毒力系统中的SctRST）的出口门运输。第四种必需的T3SS蛋白（FlhB/SctU）在生长钩/针达到确定长度时起“切换”分泌底物特异性的作用。在这里，我们展示了从鞭毛弧菌系统中提取的含有开关蛋白的出口门的低温电镜结构，分辨率为3.2 a。该结构揭示了FlhB/SctU扩展了螺旋出口门，其四个预测的跨膜螺旋包裹在FliPQR/SctRST上。FlhB/SctU螺旋的不寻常拓扑结构在关闭的出口门的底部形成了一个环路。结构信息突变表明，该环在门控分泌中至关重要，我们提出T3SS的一系列构象变化通过FlhB/SctU和FliPQR/SctRST之间的相互作用触发门的打开。
Protein secretion through type-three secretion systems (T3SS) is critical for motility and virulence of many bacteria. Proteins are transported through an export gate containing three proteins (FliPQR in flagella, SctRST in virulence systems). A fourth essential T3SS protein (FlhB/SctU) functions to "switch" secretion substrate specificity once the growing hook/needle reach their determined length. Here, we present the cryo-electron microscopy structure of an export gate containing the switch protein from a Vibrio flagellar system at 3.2 A resolution. The structure reveals that FlhB/SctU extends the helical export gate with its four predicted transmembrane helices wrapped around FliPQR/SctRST. The unusual topology of the FlhB/SctU helices creates a loop wrapped around the bottom of the closed export gate. Structure-informed mutagenesis suggests that this loop is critical in gating secretion and we propose that a series of conformational changes in the T3SS trigger opening of the gate through interactions between FlhB/SctU and FliPQR/SctRST.