A gatekeeper chaperone complex directs translocator secretion during type three secretion.
A gatekeeper chaperone complex directs translocator secretion during type three secretion.
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DOI：
10.1371/journal.ppat.1004498
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发表时间：
2014-11
期刊：
影响因子：
6.7
通讯作者：
Spiller BW
中科院分区：
文献类型：
--
作者：
Archuleta TL;Spiller BW
许多革兰氏阴性菌使用三型分泌系统(T3SS)将效应蛋白输送到宿主细胞中。这些蛋白质输送机器由识别底物并产生转位所需力量的胞液成分组成，由针状复合体和跨越基底的相关膜形成的分泌管道，以及在靶细胞中形成孔的转运体。一个明确的分泌顺序，即首先分泌针状成分蛋白，然后是转运体，最后是效应器，这是这个系统有效的必要条件。虽然不同生物体之间分泌的效应物有很大差异，但组成T3SS的∼20单个蛋白成分在许多致病细菌中是保守的。一种这样的保守蛋白质，称为塞子或看门人，对于防止不受调节的效应器释放和允许高效的转运子分泌是必要的。守门人促进转运体分泌而抑制效应器释放的机制尚不清楚。我们介绍了衣原体守门人COPN的结构，它与转运子特异的伴侣结合。该结构识别了守门人和转运子伴侣之间以前未知的界面，并揭示了在守门人-伴侣复合体中，规范的转运子结合槽可以自由结合转运子。志贺氏菌中同源复合体的结构突变表明，守门人-伴侣-转运体复合体对于转运体的分泌和转运体先于效应器的有序分泌是必不可少的。第三型分泌系统(T3SS)是许多致病革兰氏阴性菌中发现的重要毒力因子。这些机器通过将细菌蛋白质输送到宿主细胞来帮助感染，在宿主细胞中，这些蛋白质调节宿主过程，并帮助为细菌建立一个生态位。蛋白质递送以一种高度调控的方式发生，其中参与感染早期步骤的蛋白质，或建立分泌管道所必需的蛋白质，通常在其他底物之前分泌，这种现象称为分泌层次。这项研究展示了一种分子复合体的结构，它物理上将一类早期底物，即称为转运体的分泌孔成分，与一种与分泌层次有关的蛋白质联系在一起。志贺氏菌中这种相互作用的中断扰乱了转运体的分泌，同时支持效应器分泌的增加，导致表型与看门人缺失难以区分，并导致得出结论，看门人-伴侣-转运体复合体是T3SS的关键组成部分。
Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ∼20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors. Type Three Secretion Systems (T3SS) are essential virulence factors found in many pathogenic Gram-negative bacteria. These machines aid infection by delivering bacterial proteins into host cells where these proteins modulate host processes and help establish a niche for the bacteria. Protein delivery occurs in a highly regulated manner in which proteins involved in early steps in infection, or necessary to build the secretion conduit, are typically secreted before other substrates, a phenomenon termed secretion hierarchy. This study presents the structure of a molecular complex that physically links one class of early substrates, components of the secretion pore termed translocators, to a gatekeeper protein, a protein that has been implicated in the secretion hierarchy. Disruption of this interaction in Shigella disrupts the secretion of translocators, while supporting increased secretion of effectors, resulting in phenotypes indistinguishable from a gatekeeper deletion, and leading to the conclusion that a gatekeeper-chaperone-translocator complex is a critical component of the T3SS.
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影响因子：
3.6
作者：
Fields, KA;Hackstadt, T
通讯作者：
Hackstadt, T
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16
作者：
Birtalan, SC;Phillips, RM;Ghosh, P
通讯作者：
Ghosh, P
影响因子：
3.6
作者：
Cherradi, Youness;Schiavolin, Lionel;Botteaux, Anne
通讯作者：
Botteaux, Anne
影响因子：
4.8
作者：
Job, Viviana;Mattei, Pierre-Jean;Dessen, Andrea
通讯作者：
Dessen, Andrea