Catch and arrest: exploiting the retromer by a Chlamydial effector.
Catch and arrest: exploiting the retromer by a Chlamydial effector.
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DOI：
10.1038/sigtrans.2017.39
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发表时间：
2017
影响因子：
39.3
通讯作者：
Luo ZQ
中科院分区：
文献类型：
--
作者：
Luo ZQ
专性细菌病原体沙眼衣原体是性传播疾病的主要原因；它通过建立一个称为包涵体的区室在宿主细胞中增殖。 2 内含物的生物发生需要大量效应蛋白，这些蛋白可能通过 III 型分泌系统 (T3SS) 转位到宿主细胞中。 2, 3 这些效应器通过与宿主蛋白相互作用来调节各种宿主细胞过程，特别是那些参与囊泡运输的蛋白。 2 已鉴定出 50 多个针对沙眼衣原体的 T3SS 效应子，其中大多数与已知活性的蛋白质几乎没有同源性，也不包含暗示潜在功能的可预测结构基序。 4 目前可用的生物信息学工具可预测的与细菌效应子相关的活性的缺乏可以说是这些蛋白质功能解析中的最大挑战。 2, 3 通过对宿主细胞中瞬时表达的效应子进行亲和纯化，已鉴定出 30 多种衣原体效应子的潜在宿主靶标。 5 其中，IncE 被发现与分选连接蛋白 (SNX) 5/6（逆转录体的组成部分）相互作用，5 是由五种不同蛋白质（异五聚体）形成的复合物，通过介导跨膜货物从内体到目的地（例如跨高尔基体隔室）的逆行运输，参与广泛的细胞过程。 6 删除分析显示，IncE 结合分选连接蛋白 5 (SNX5-PX) 的 Phox 结构域，该区域参与结合信号脂质磷脂酰肌醇 3-磷酸。 5 三项结构研究表明，该效应子特异性识别 SNX5 PX 结构域上高度保守的疏水沟。 1, 7, 8 引人注目的是，这些研究均确定了位于 IncE 羧基末端的 26 个残基区域 (IncE107-132) 作为直接与 SNX5 结合的位点（图 1），强调了这个胞质暴露结构域在宿主蛋白招募中的重要性。 IncE107–132–SNX522– 的高分辨率结构
The obligate bacterial pathogen Chlamydia trachomatis is a major cause of sexually transmitted diseases; it proliferates in host cells by establishing a compartment called inclusion. 2 The biogenesis of the inclusion requires a large cohort of effector proteins that are translocated into the host cell, presumably by a type III secretion system (T3SS). 2, 3 These effectors modulate various host cell processes by interacting with host proteins, particularly those involved in vesicle trafficking. 2 More than 50 T3SS effectors have been identified for C. trachomatis, most of which share little homology with proteins of known activity, nor do they harbor predictable structural motifs suggestive of potential function. 4 The lack of activity associated with bacterial effectors predicable by currently available bioinformatics tools is arguably the biggest challenge in functional dissection of these proteins. 2, 3 By affinity purification of effectors transiently expressed in host cells, the potential host targets for more than 30 Chlamydial effectors had been identified. 5 Among these, IncE was found to interact with sorting nexins (SNXs) 5/6, components of the retromer, 5 which is a complex formed by five different proteins (heteropentamer) that participates in a wide range of cellular processes by mediating retrograde transport of transmembrane cargo from endosomes to destinations such as the trans-Golgi compartment. 6Deletion analysis revealed that IncE binds the Phox domain of sorting nexin 5 (SNX5-PX), a region involved in binding the signaling lipid phosphatidylinositol 3-phosphate. 5 The three structural studies showed that this effector specifically recognizes a highly conserved hydrophobic groove on the PX domain of SNX5. 1, 7, 8 Strikingly, each of these studies identified a 26-residue region (IncE107–132) localized in the carboxyl end of IncE as the site that directly engages SNX5 (Figure 1), highlighting the importance of this cytosolically exposed domain in the recruitment of the host protein. The high-resolution structures of the IncE107–132–SNX522–
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分类 nexin 5/6 与细菌效应器 IncE 相互作用的结构和功能见解
影响因子：
39.3
作者：
Sun Q;Yong X;Sun X;Yang F;Dai Z;Gong Y;Zhou L;Zhang X;Niu D;Dai L;Liu JJ;Jia D
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Jia D
影响因子：
30.3
作者：
Mirrashidi KM;Elwell CA;Verschueren E;Johnson JR;Frando A;Von Dollen J;Rosenberg O;Gulbahce N;Jang G;Johnson T;Jäger S;Gopalakrishnan AM;Sherry J;Dunn JD;Olive A;Penn B;Shales M;Cox JS;Starnbach MN;Derre I;Valdivia R;Krogan NJ;Engel J
通讯作者：
Engel J
影响因子：
7.7
作者：
Paul, Blessy;Kim, Hyun Sung;Collins, Brett M.
通讯作者：
Collins, Brett M.
DOI：
10.1038/nrmicro3160
发表时间：
2014-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Huang J;Brumell JH
通讯作者：
Brumell JH
DOI：
10.1038/nrmicro.2016.30
发表时间：
2016-06
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Elwell C;Mirrashidi K;Engel J
通讯作者：
Engel J