小柯机器人

西班牙国家癌症研究中心Oscar Llorca和德国朱利叶斯-马克西米利安大学WrzburgSebastian Geibel团队合作，解析了分枝杆菌VII型分泌系统的结构。 2019年10月9日，《自然》在线发表了这项成果。

研究人员解析了耻垢分枝杆菌的ESX-3 / VII型分泌系统膜包埋核心复合物分辨率为3.7Å的冷冻电镜结构。 ESX-3分泌系统的核心是由化学计量比为1：1：2：1的EccB3：EccC3：EccD3：EccE3四种蛋白质组成，并且构建了两个相同的启动子。 EccC3偶联蛋白由包含四个ATPase结构域的柔性序列组成，这些结构域通过茎域与膜连接。靠近茎的“未知功能结构域”（DUF）是分泌ATPase的必需结构域。 EccB3主要是周质的，但有一小段穿过膜并与茎结构域接触，这表明EccC3远端与底物结合和随后DUF中ATP水解触发的茎结构域构象变化，可能与底物分泌到周质有关。

该研究结果表明，VII型分泌系统的体系结构明显不同于其他已知的分泌系统。

据了解，VII型分泌系统分泌的毒力因子促进了病原性分枝杆菌（如结核分枝杆菌）对宿主感染。

附：英文原文

Title: Architecture of the mycobacterial type VII secretion system

Author: Nikolaos Famelis, Angel Rivera-Calzada, Gianluca Degliesposti, Maria Wingender, Nicole Mietrach, J. Mark Skehel, Rafael Fernandez-Leiro, Bettina Bttcher, Andreas Schlosser, Oscar Llorca, Sebastian Geibel

Issue&Volume: 2019-10-09

Abstract: 

Host infection by pathogenic mycobacteria such as Mycobacterium tuberculosis is facilitated by virulence factors secreted by type VII secretion systems1. Here we report the cryo-electron microscopy structure of a membrane-embedded core complex of the ESX-3/type VII secretion system from Mycobacterium smegmatis at 3.7 Å resolution. The core of the ESX-3 secretion machine consists of four protein components, EccB3:EccC3:EccD3:EccE3 in a 1:1:2:1 stoichiometry, building two identical protomers. The EccC3 coupling protein comprises a flexible array of four ATPase domains, which are linked to the membrane through a stalk domain. The ‘domain of unknown function’ (DUF) adjacent to the stalk is identified as an ATPase domain essential for secretion. EccB3 is predominantly periplasmatic but a small segment crosses the membrane and contacts the stalk domain, suggesting that conformational changes in the stalk domain triggered by substrate binding at the distal end of EccC3 and subsequent ATP hydrolysis in the DUF could be coupled to substrate secretion to the periplasm. Our results reveal that the architecture of type VII secretion systems differs markedly from other known secretion machines2.

DOI: 10.1038/s41586-019-1633-1

Source:https://www.nature.com/articles/s41586-019-1633-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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