分枝杆菌 ESX-1、ESX-3 和 ESX-5 型 VII 分泌系统中 EspG 伴侣蛋白的结构变异性。
Structural Variability of EspG Chaperones from Mycobacterial ESX-1, ESX-3, and ESX-5 Type VII Secretion Systems.
机构信息
European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22607, Germany.
UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
出版信息
J Mol Biol. 2019 Jan 18;431(2):289-307. doi: 10.1016/j.jmb.2018.11.003. Epub 2018 Nov 10.
Type VII secretion systems (ESX) are responsible for transport of multiple proteins in mycobacteria. How different ESX systems achieve specific secretion of cognate substrates remains elusive. In the ESX systems, the cytoplasmic chaperone EspG forms complexes with heterodimeric PE-PPE substrates that are secreted from the cells or remain associated with the cell surface. Here we report the crystal structure of the EspG chaperone from the ESX-1 system determined using a fusion strategy with T4 lysozyme. EspG adopts a quasi 2-fold symmetric structure that consists of a central β-sheet and two α-helical bundles. In addition, we describe the structures of EspG chaperones from four different crystal forms. Alternate conformations of the putative PE-PPE binding site are revealed by comparison of the available EspG structures. Analysis of EspG, EspG, and EspG chaperones using small-angle X-ray scattering reveals that EspG and EspG chaperones form dimers in solution, which we observed in several of our crystal forms. Finally, we propose a model of the ESX-3 specific EspG-PE5-PPE4 complex based on the small-angle X-ray scattering analysis.
VII 型分泌系统（ESX）负责将多种蛋白质运输到分枝杆菌中。不同的 ESX 系统如何实现同源底物的特异性分泌仍然难以捉摸。在 ESX 系统中，细胞质伴侣蛋白 EspG 与异二聚体 PE-PPE 底物形成复合物，这些底物从细胞中分泌出来或仍然与细胞表面相关联。在这里，我们报告了使用与 T4 溶菌酶融合策略确定的 ESX-1 系统中 EspG 伴侣蛋白的晶体结构。EspG 采用准 2 倍对称结构，由中心β-折叠和两个α-螺旋束组成。此外，我们还描述了来自四种不同晶体形式的 EspG 伴侣蛋白的结构。通过比较可用的 EspG 结构，揭示了假定的 PE-PPE 结合位点的交替构象。使用小角度 X 射线散射分析 EspG、EspG 和 EspG 伴侣蛋白表明，EspG 和 EspG 伴侣蛋白在溶液中形成二聚体，我们在几个晶体形式中观察到了这一点。最后，我们根据小角度 X 射线散射分析提出了基于 ESX-3 特异性 EspG-PE5-PPE4 复合物的模型。
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