CsrA-FliW interaction governs flagellin homeostasis and a checkpoint on flagellar morphogenesis in Bacillus subtilis.
CsrA-FliW interaction governs flagellin homeostasis and a checkpoint on flagellar morphogenesis in Bacillus subtilis.
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DOI：
10.1111/j.1365-2958.2011.07822.x
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Kearns DB
中科院分区：
文献类型：
--
作者：
Mukherjee S;Yakhnin H;Kysela D;Sokoloski J;Babitzke P;Kearns DB
CsrA是一种广泛分布的RNA结合蛋白，可调控靶转录物的翻译起始和/或mRNA稳定性。在几种革兰氏阴性细菌中，含有多个CsrA结合位点的sRNA可拮抗CsrA活性。在这里，我们发现flw，第一个CsrA活性的蛋白拮抗剂，在革兰氏阳性菌枯草芽孢杆菌中构成伴侣转换机制来控制鞭毛蛋白的合成。在钩完成的鞭毛组装检查点之后，鞭毛蛋白（Hag）的分泌从FliW-Hag复合物中释放FliW蛋白。FliW随后与CsrA结合，减轻CsrA介导的hag对鞭毛蛋白合成和细丝组装的翻译抑制。因此，鞭毛蛋白动态地限制了它自己的翻译。稳态自调节可能是精确控制特定时间和有限数量所需的结构亚基的一般机制，如鞭毛、III型分泌机器和毛的组装。最后，系统发育分析表明，在许多细菌病原体中具有高度多效性的毒力调节剂CsrA在鞭毛组装中具有祖先作用，并进化为共同调节各种细胞运动过程。
CsrA is a widely distributed RNA binding protein that regulates translation initiation and/or mRNA stability of target transcripts. CsrA activity is antagonized by sRNA(s) containing multiple CsrA binding sites in several Gram-negative bacterial species. Here we discover FliW, the first protein antagonist of CsrA activity that constitutes a partner switching mechanism to control flagellin synthesis in the Gram-positive organism Bacillus subtilis. Following the flagellar assembly checkpoint of hook completion, secretion of flagellin (Hag) releases FliW protein from a FliW-Hag complex. FliW then binds to CsrA and relieves CsrA-mediated translational repression of hag for flagellin synthesis concurrent with filament assembly. Thus, flagellin homeostatically restricts its own translation. Homeostatic autoregulation may be a general mechanism to precisely control structural subunits required at specific times and in finite amounts such as those involved in the assembly of flagella, type III secretion machines, and pili. Finally, phylogenetic analysis suggests that CsrA, a highly pleiotropic virulence regulator in many bacterial pathogens, had an ancestral role in flagellar assembly and evolved to co-regulate various cellular processes with motility.