Structure of the mycobacterial ESX-5 type VII secretion system pore complex.

Structure of the mycobacterial ESX-5 type VII secretion system pore complex.
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分枝杆菌ESX-5 VII型分泌系统孔复合物的结构。

DOI:
10.1126/sciadv.abg9923
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发表时间:
2021-06
期刊:
影响因子:
13.6
通讯作者:
Wilmanns M
Wilmanns M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Beckham KSH;Ritter C;Chojnowski G;Ziemianowicz DS;Mullapudi E;Rettel M;Savitski MM;Mortensen SA;Kosinski J;Wilmanns M

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分枝杆菌ESX-5分泌系统的结构揭示了中央跨膜孔。ESX-5 VII型分泌系统是分枝杆菌病原体毒力的关键跨膜蛋白复合物。然而,完全组装的易位机制的整体架构和中央分泌孔的组成仍然未知。在这里,我们提出了2.1兆道尔顿ESX-5核心复杂的高分辨率结构。我们的结构捕获了一个动态的,分泌能力的构象孔内一个明确的跨膜部分,夹在两个灵活的蛋白质层在胞质入口和周质出口。我们建议,这种灵活性赋予的ESX-5机器与大的构象可塑性,以适应靶向蛋白质分泌。与已知的分泌系统相比,孔的高度动态状态可能代表细菌分泌机制的基本原理。
The structure of the mycobacterial ESX-5 secretion system reveals a central transmembrane pore. The ESX-5 type VII secretion system is a membrane-spanning protein complex key to the virulence of mycobacterial pathogens. However, the overall architecture of the fully assembled translocation machinery and the composition of the central secretion pore have remained unknown. Here, we present the high-resolution structure of the 2.1-megadalton ESX-5 core complex. Our structure captured a dynamic, secretion-competent conformation of the pore within a well-defined transmembrane section, sandwiched between two flexible protein layers at the cytosolic entrance and the periplasmic exit. We propose that this flexibility endows the ESX-5 machinery with large conformational plasticity required to accommodate targeted protein secretion. Compared to known secretion systems, a highly dynamic state of the pore may represent a fundamental principle of bacterial secretion machineries.
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