Recognition and targeting mechanisms by chaperones in flagellum assembly and operation
Recognition and targeting mechanisms by chaperones in flagellum assembly and operation
复制标题
DOI：
10.1073/pnas.1607845113
复制
发表时间：
2016-08-30
影响因子：
11.1
通讯作者：
Kalodimos, Charalampos G.
中科院分区：
文献类型：
--
作者：
Khanra, Nandish;Rossi, Paolo;Kalodimos, Charalampos G.
鞭毛是一种复杂的细菌纳米机器，需要几种不同蛋白质的适当组装才能发挥其功能。专用的分子伴侣在防止鞭毛蛋白的聚集或不期望的相互作用，包括它们靶向出口门中是中心的。FliT是一种关键的鞭毛分子伴侣，其与细胞质中的几种鞭毛蛋白结合，包括其同源的毒力加帽蛋白FliD。我们已经确定了溶液结构的FliT分子伴侣在自由状态和复杂的FliD和鞭毛ATP酶FliI。FliT采用四螺旋束，并使用由前三个螺旋形成的疏水表面来识别其底物蛋白。我们发现，第四螺旋构成的结合位点FlhA，膜蛋白在出口门。在不存在底物蛋白的情况下，FliT采用自抑制结构，其中底物和FlhA的结合位点都被封闭。底物与FliT的结合激活复合物的FlhA结合，从而使伴侣-底物复合物靶向输出门。FliT报告的激活和靶向机制似乎在其他鞭毛分子伴侣之间共享。
The flagellum is a complex bacterial nanomachine that requires the proper assembly of several different proteins for its function. Dedicated chaperones are central in preventing aggregation or undesired interactions of flagellar proteins, including their targeting to the export gate. FliT is a key flagellar chaperone that binds to several flagellar proteins in the cytoplasm, including its cognate filament-capping protein FliD. We have determined the solution structure of the FliT chaperone in the free state and in complex with FliD and the flagellar ATPase FliI. FliT adopts a four-helix bundle and uses a hydrophobic surface formed by the first three helices to recognize its substrate proteins. We show that the fourth helix constitutes the binding site for FlhA, a membrane protein at the export gate. In the absence of a substrate protein FliT adopts an autoinhibited structure wherein both the binding sites for substrates and FlhA are occluded. Substrate binding to FliT activates the complex for FlhA binding and thus targeting of the chaperone-substrate complex to the export gate. The activation and targeting mechanisms reported for FliT appear to be shared among the other flagellar chaperones.