Identification of the DotL coupling protein subcomplex of the Legionella Dot/Icm type IV secretion system.

Identification of the DotL coupling protein subcomplex of the Legionella Dot/Icm type IV secretion system.
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DOI:
10.1111/j.1365-2958.2012.08118.x
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发表时间:
2012-07
影响因子:
3.6
通讯作者:
Vogel JP
Vogel JP
中科院分区:
生物学2区
文献类型:
--
作者:
Vincent CD;Friedman JR;Jeong KC;Sutherland MC;Vogel JP

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嗜肺军团菌是军团病的病原体,通过改变宿主细胞的内吞途径在巨噬细胞中存活。为了实现这一点,细菌利用IVB型分泌系统将效应分子递送到宿主细胞质中。在以前的报告中,我们进行了广泛的表征L。pneumophila型IVB分泌系统,导致鉴定了形成分泌装置核心的关键五蛋白亚复合物。在这里,我们描述了第二点/Icm蛋白亚组组成的IV型偶联蛋白DotL,仪器蛋白DotM和DotN,和分泌衔接蛋白IcmS和IcmW。在不存在IcmS或IcmW的情况下,DotL在从生长的指数期到稳定期的过渡时变得不稳定,同时表达许多分泌的底物。DotL的丧失依赖于ClpA,ClpA是细胞质蛋白酶ClpP的调节剂。icmS和icmW突变体中DotL水平的降低加剧了这些菌株的细胞内缺陷,并且可以通过DotL的过度产生而部分抑制。因此,除了它们作为军团菌T4 SS底物的分子伴侣的作用之外,IcmS和IcmW作为Dot/Icm IV型偶联蛋白亚复合物的一部分执行第二功能。
Legionella pneumophila, the causative agent of Legionnaires’ disease, survives in macrophages by altering the endocytic pathway of its host cell. To accomplish this, the bacterium utilizes a type IVB secretion system to deliver effector molecules into the host cell cytoplasm. In a previous report, we performed an extensive characterization of the L. pneumophila type IVB secretion system that resulted in the identification of a critical five-protein subcomplex that forms the core of the secretion apparatus. Here we describe a second Dot/Icm protein subassembly composed of the type IV coupling protein DotL, the apparatus proteins DotM and DotN, and the secretion adaptor proteins IcmS and IcmW. In the absence of IcmS or IcmW, DotL becomes destabilized at the transition from the exponential to stationary phases of growth, concurrent with the expression of many secreted substrates. Loss of DotL is dependent on ClpA, a regulator of the cytoplasmic protease ClpP. The resulting decreased levels of DotL in the icmS and icmW mutants exacerbates the intracellular defects of these strains and can be partially suppressed by overproduction of DotL. Thus, in addition to their role as chaperones for Legionella T4SS substrates, IcmS and IcmW perform a second function as part of the Dot/Icm type IV coupling protein subcomplex.
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