Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar.
Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar.
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DOI：
10.1371/journal.ppat.1002386
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发表时间：
2011-11
期刊：
影响因子：
6.7
通讯作者：
Cascales E
中科院分区：
文献类型：
--
作者：
Felisberto-Rodrigues C;Durand E;Aschtgen MS;Blangy S;Ortiz-Lombardia M;Douzi B;Cambillau C;Cascales E
VI型分泌系统(T6SS)是一种跨包膜的机器，致力于将毒力因子分泌到真核或原核细胞中，因此是致病和/或与邻近细菌竞争所必需的。T6SS装置类似于噬菌体T4的注射装置，通过膜复合体固定在细胞膜上。该膜复合体由TSSl、TssM和TagL内膜锚定蛋白和TssJ外膜脂蛋白组成。在这里，我们报道了肠聚集性大肠杆菌Sci1TssJ脂蛋白的晶体结构，这是一种两个四链的β-Sheet蛋白，它显示一个带有额外的α-螺旋结构域的跨甲状腺素折叠和一个突出的环。我们发现TssJ通过这个环与TssM接触，因为环耗尽的突变体在体外或体内都无法与TssM相互作用。对TssM和TssJ-TssM相互作用的生物物理分析提出了T6SS的膜锚定外壳的结构模型。总而言之，我们的结果提供了对T6SS组装的更好的理解，并鼓励针对T6SS的新型抗菌剂的结构辅助药物设计。VI型分泌系统(T6SS)是一种专门的分泌机器，负责运输毒力因子。T6s是多种多样的，因为它们能够靶向真核和原核细胞。因此，它们通过直接作用于宿主，以及从生态位中消除竞争细菌，在致病过程中发挥着重要作用。在分子水平上，T6SS至少由13种称为核心成分的蛋白质组成，所有这些蛋白质都是分泌系统活动所必需的。这些核心成分可以分为两类：与噬菌体T4亚基具有共同进化历史的可溶性蛋白，以及将噬菌体样结构锚定到包膜上所需的膜或膜相关蛋白。在这里，我们报告了膜相关的核心成分之一，TssJ脂蛋白的晶体结构。该结构显示出一个补充了额外结构元素的跨甲状腺激素折叠。其中之一是连接两条β链的环，负责TssJ脂蛋白与内膜蛋白TssM的C末端结构域的相互作用。我们认为这两个蛋白质连接了两个膜，形成了一个通道来容纳噬菌体的结构。这些结果为了解这些分泌器的生物起源提供了重要的新见解。
Type VI secretion systems (T6SS) are trans-envelope machines dedicated to the secretion of virulence factors into eukaryotic or prokaryotic cells, therefore required for pathogenesis and/or for competition towards neighboring bacteria. The T6SS apparatus resembles the injection device of bacteriophage T4, and is anchored to the cell envelope through a membrane complex. This membrane complex is composed of the TssL, TssM and TagL inner membrane anchored proteins and of the TssJ outer membrane lipoprotein. Here, we report the crystal structure of the enteroaggregative Escherichia coli Sci1 TssJ lipoprotein, a two four-stranded β-sheets protein that exhibits a transthyretin fold with an additional α-helical domain and a protruding loop. We showed that TssJ contacts TssM through this loop since a loop depleted mutant failed to interact with TssM in vitro or in vivo. Biophysical analysis of TssM and TssJ-TssM interaction suggest a structural model of the membrane-anchored outer shell of T6SS. Collectively, our results provide an improved understanding of T6SS assembly and encourage structure-aided drug design of novel antimicrobials targeting T6SS. Type VI secretion systems (T6SS) are specialized secretion machines responsible for the transport of virulence factors. T6SS are versatile as they are able to target both eukaryotic and prokaryotic cells. They therefore play an important role in pathogenesis by acting directly on the host, as well as eliminating competing bacteria from the niche. At a molecular level, T6SS are composed of a minimum of 13 proteins called core-components, all required for the activity of the secretion system. These core-components can be divided in two groups: soluble proteins having a common evolution history with bacteriophage T4 subunits, and membrane or membrane-associated proteins required for anchoring the bacteriophage-like structure to the envelope. Here, we report the crystal structure of one of the membrane-associated core component, the TssJ lipoprotein. The structure exhibits a transthyretin fold supplemented with additional structural elements. One of these, a loop connecting two beta-strands, is responsible for the interaction of the TssJ lipoprotein with the C-terminal domain of the inner membrane protein TssM. We propose that these two proteins link the two membranes and form a channel accommodating the bacteriophage-like structure. These results provide important new insights to understand the biogenesis of these secretion apparati.
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影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
Barton GJ
影响因子：
5.8
作者：
Gouet, P;Courcelle, E;Métoz, F
通讯作者：
Métoz, F
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：
3.6
作者：
Crago, AM;Koronakis, V
通讯作者：
Koronakis, V
DOI：
10.1107/s0907444904016427
发表时间：
2004-12-01
影响因子：
2.2
作者：
Blanc, E;Roversi, P;Bricogne, G
通讯作者：
Bricogne, G