Polar assembly and scaffolding proteins of the virulence-associated ESX-1 secretory apparatus in mycobacteria.
Polar assembly and scaffolding proteins of the virulence-associated ESX-1 secretory apparatus in mycobacteria.
复制标题
分枝杆菌毒力相关 ESX-1 分泌装置的极性组装和支架蛋白。
DOI：
10.1111/j.1365-2958.2011.07958.x
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发表时间：
2012
影响因子：
3.6
通讯作者：
Derbyshire,KeithM
中科院分区：
文献类型：
--
作者：
Wirth,SamanthaE;Krywy,JanetA;Aldridge,BreeB;Fortune,SarahM;Fernandez-Suarez,Marta;Gray,ToddA;Derbyshire,KeithM
ESX‐1分泌系统是结核分枝杆菌（Mtb）致病性所必需的。尽管进行了大量的研究，但对ESX - 1的结构成分知之甚少，也不知道这些蛋白质是如何组装成活性分泌装置的。在这里，我们利用耻垢分枝杆菌（Ms）功能相关的ESX‐1装置来证明，ESX‐1活性所需的荧光标记蛋白始终定位于细胞极，通过时间推移荧光显微镜鉴定为非间隔（旧）极。msesx1的缺失阻止了标记蛋白的极性定位，表明在极性运输中需要特定的蛋白质相互作用。值得注意的是，MtbESX - 1基因座在MtbESX - 1突变体中的表达恢复了标记蛋白的极性定位，这表明MtbESX - 1基因座在m .垢垢菌中的建立。这一观察结果说明了控制ESX - 1组装的蛋白质相互作用的跨物种保护，以及极性定位。重要的是，我们描述了新的非esx1编码蛋白，它们影响ESX‐1的活性，与ESX‐1共定位，并且是ESX‐1募集和组装所必需的。这一分析为这一重要的毒力决定因素的分子组装提供了新的见解。
The ESX‐1 secretion system is required for pathogenicity ofMycobacterium tuberculosis(Mtb). Despite considerable research, little is known about the structural components of ESX‐1, or how these proteins are assembled into the active secretion apparatus. Here, we exploit the functionally related ESX‐1 apparatus ofMycobacterium smegmatis(Ms) to show that fluorescently tagged proteins required for ESX‐1 activity consistently localize to the cell pole, identified by time‐lapse fluoro‐microscopy as the non‐septal (old) pole. Deletions inMsesx1prevented polar localization of tagged proteins, indicating the need for specific protein–protein interactions in polar trafficking. Remarkably, expression of theMtbesx1locus inMsesx1mutants restored polar localization of tagged proteins, indicating establishment of the MtbESX‐1 apparatus inM. smegmatis. This observation illustrates the cross‐species conservation of protein interactions governing assembly of ESX‐1, as well as polar localization. Importantly, we describe novel non‐esx1‐encoded proteins, which affect ESX‐1 activity, which colocalize with ESX‐1, and which are required for ESX‐1 recruitment and assembly. This analysis provides new insights into the molecular assembly of this important determinant ofMtbvirulence.