Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer.
Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer.
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DOI：
10.1111/mmi.12770
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发表时间：
2014-10
影响因子：
3.6
通讯作者：
Korotkov KV
中科院分区：
文献类型：
--
作者：
Korotkova N;Freire D;Phan TH;Ummels R;Creekmore CC;Evans TJ;Wilmanns M;Bitter W;Parret AH;Houben EN;Korotkov KV
结核分枝杆菌的生长或毒力依赖于同源的VII型分泌系统，ESX-1、ESX-3和ESX-5，它们输出许多蛋白效应器穿过膜到达细菌表面和环境。PE和PPE蛋白代表了两个由ESX系统分泌的高度多态性蛋白大家族。最近，研究表明这些蛋白需要系统特异性的细胞质伴侣来分泌。在这里，我们报道了结核分枝杆菌esx -5分泌的pe25 - pep41异源二聚体与细胞质伴侣EspG5复合物的晶体结构。EspG5代表了一种新的折叠，与先前表征的分泌伴侣蛋白无关。通过对espg5结合区域的功能分析，发现PPE41上存在一个疏水斑块，促进二聚体聚集，而伴侣蛋白有效地消除了这一过程。我们发现，PPE41含有一个典型的伴侣结合序列，即hh基序，该序列在ESX-1、ESX-3和esx -5特异性PPE蛋白中高度保守。通过引入不同的点突变破坏EspG5与三种不同PPE靶蛋白之间的相互作用通常会影响蛋白分泌。我们进一步证明，EspG5伴侣通过保持易于聚集的PE-PPE蛋白处于可溶性状态，在ESX分泌机制中发挥重要作用。
The growth or virulence of Mycobacterium tuberculosis bacilli depends on homologous type VII secretion systems, ESX-1, ESX-3 and ESX-5, which export a number of protein effectors across membranes to the bacterial surface and environment. PE and PPE proteins represent two large families of highly polymorphic proteins that are secreted by these ESX systems. Recently, it was shown that these proteins require system-specific cytoplasmic chaperones for secretion. Here, we report the crystal structure of M. tuberculosis ESX-5-secreted PE25–PPE41 heterodimer in complex with the cytoplasmic chaperone EspG5. EspG5 represents a novel fold that is unrelated to previously characterized secretion chaperones. Functional analysis of the EspG5-binding region uncovered a hydrophobic patch on PPE41 that promotes dimer aggregation, and the chaperone effectively abolishes this process. We show that PPE41 contains a characteristic chaperone-binding sequence, the hh motif, which is highly conserved among ESX-1-, ESX-3- and ESX-5-specific PPE proteins. Disrupting the interaction between EspG5 and three different PPE target proteins by introducing different point mutations generally affected protein secretion. We further demonstrate that the EspG5 chaperone plays an important role in the ESX secretion mechanism by keeping aggregation-prone PE–PPE proteins in their soluble state.
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DOI：
10.1073/pnas.1119453109
发表时间：
2012-07-10
影响因子：
11.1
作者：
Daleke, Maria H.;Ummels, Roy;Bitter, Wilbert
通讯作者：
Bitter, Wilbert
影响因子：
16
作者：
Birtalan, SC;Phillips, RM;Ghosh, P
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Ghosh, P
DOI：
10.1107/s090744490903947x
发表时间：
2010-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Cowtan K
通讯作者：
Cowtan K
DOI：
10.1016/j.bbamcr.2013.12.019
发表时间：
2014-08
影响因子：
5.1
作者：
Christie, Peter J.;Whitaker, Neal;Gonzalez-Rivera, Christian
通讯作者：
Gonzalez-Rivera, Christian
影响因子：
6.4
作者：
Bottai, Daria;Majlessi, Laleh;Brosch, Roland
通讯作者：
Brosch, Roland