Coevolution of the ATPase ClpV, the sheath proteins TssB and TssC, and the accessory protein TagJ/HsiE1 distinguishes type VI secretion classes.
Coevolution of the ATPase ClpV, the sheath proteins TssB and TssC, and the accessory protein TagJ/HsiE1 distinguishes type VI secretion classes.
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DOI：
10.1074/jbc.m114.600510
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发表时间：
2014-11-21
期刊：
影响因子：
--
通讯作者：
Filloux A
中科院分区：
文献类型：
--
作者：
Förster A;Planamente S;Manoli E;Lossi NS;Freemont PS;Filloux A
背景：细菌VI型分泌器是分泌毒素/效应物的噬菌体尾样结构。结果：VI型分泌系统的四个组分相互作用，共同进化。结论：不同类别的VI型分泌系统出现的系统发育数据。意义：对VI型分泌的分子理解可能使其适合于抗微生物剂的靶向。VI型分泌系统（T6 SS）是用于将效应分子转运到原核和真核细胞中的细菌纳米机器。它涉及由TssB和TssC组成的管状结构的组装，其类似于噬菌体的尾鞘。鞘管收缩以提供效应器输送所需的能量。AAA+ ATP酶ClpV拆卸收缩的鞘管，从而重置系统，以便重新组装准备再次击发的延长鞘管。这种机制对T6 SS功能至关重要。在霍乱弧菌中，ClpV在疏水沟内结合TssC的N末端。在这项研究中，我们解决了铜绿假单胞菌ClpV 1的N-末端结构域的晶体结构，并观察到疏水沟的结构改变。在ClpV 1沟的修改相匹配的TssC的N末端的变化，表明存在不同的T6 SS类。一个附属的T6 SS组件，TagJ/HsiE，主要存在于其中一个类。使用细菌双杂交方法，我们发现铜绿假单胞菌同源物HsiE 1与ClpV 1强烈相互作用。然后，我们解决了HsiE 1的晶体结构与HsiB 1，TssB同源物和收缩鞘的组成部分的N末端的复合物。系统发育分析证实，这些差异区分T6 SS类，导致TssB，TssC，TagJ/HsiE，和ClpV之间的功能性共同进化。TagJ/HsiE与鞘以及与ClpV的相互作用表明HsiE将ATP酶招募到鞘的另一种分解模式。
Background: The bacterial type VI secretion apparatus is a phage tail-like structure that secretes toxins/effectors. Results: Four components of the type VI secretion system have coevolved and interact. Conclusion: Distinct classes of type VI secretion systems emerge from the phylogenetic data. Significance: Molecular understanding of type VI secretion might make it amenable to targeting by antimicrobials. The type VI secretion system (T6SS) is a bacterial nanomachine for the transport of effector molecules into prokaryotic and eukaryotic cells. It involves the assembly of a tubular structure composed of TssB and TssC that is similar to the tail sheath of bacteriophages. The sheath contracts to provide the energy needed for effector delivery. The AAA+ ATPase ClpV disassembles the contracted sheath, which resets the systems for reassembly of an extended sheath that is ready to fire again. This mechanism is crucial for T6SS function. In Vibrio cholerae, ClpV binds the N terminus of TssC within a hydrophobic groove. In this study, we resolved the crystal structure of the N-terminal domain of Pseudomonas aeruginosa ClpV1 and observed structural alterations in the hydrophobic groove. The modification in the ClpV1 groove is matched by a change in the N terminus of TssC, suggesting the existence of distinct T6SS classes. An accessory T6SS component, TagJ/HsiE, exists predominantly in one of the classes. Using bacterial two-hybrid approaches, we showed that the P. aeruginosa homolog HsiE1 interacts strongly with ClpV1. We then resolved the crystal structure of HsiE1 in complex with the N terminus of HsiB1, a TssB homolog and component of the contractile sheath. Phylogenetic analysis confirmed that these differences distinguish T6SS classes that resulted from a functional co-evolution between TssB, TssC, TagJ/HsiE, and ClpV. The interaction of TagJ/HsiE with the sheath as well as with ClpV suggests an alternative mode of disassembly in which HsiE recruits the ATPase to the sheath.