Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis
Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis
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DOI：
10.1038/nmicrobiol.2017.47
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发表时间：
2017-06-01
影响因子：
28.3
通讯作者：
Houben, Edith N. G.
中科院分区：
文献类型：
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作者：
Beckham, Katherine S. H.;Ciccarelli, Luciano;Houben, Edith N. G.
分枝杆菌的特征在于它们的不渗透性外膜，其富含分枝菌酸。为了将底物运输穿过这种复杂的细胞包膜，分枝杆菌依赖于VII型（也称为ESX）分泌系统。在结核分枝杆菌中，这些ESX系统对于生长和完全毒力是必不可少的，因此代表了抗结核药物的有吸引力的靶标。然而，由于缺乏结构信息，VII型分泌的分子细节在很大程度上是未知的。在这里，我们报告的ESX-5膜复合物的分子结构，从分枝杆菌xenopi确定在13埃分辨率的电子显微镜。ESX-5复合物的四种核心蛋白（EccB（5）、EccC（5）、EccD（5）和EccE（5））以等摩尔化学计量组装成显示六重对称性的寡聚体组装体。这种膜相关复合物似乎专门嵌入内膜中，这表明需要额外的成分才能将底物转运穿过分枝杆菌外膜。此外，EccC ATP酶的扩展胞质结构域与分泌效应物相互作用，是高度灵活的，这表明了一种尚未看到的底物相互作用模式。我们的结果与其他细菌分泌系统的已知结构的比较表明，VII型分泌系统的架构是根本不同的，这表明一种替代的分泌机制。
Mycobacteria are characterized by their impermeable outermembrane, which is rich in mycolic acids. To transport substrates across this complex cell envelope, mycobacteria rely on type VII (also known as ESX)secretion systems. In Mycobacterium tuberculosis, these ESX systems are essential for growth and full virulence and therefore represent an attractive target for anti-tuberculosis drugs. However, the molecular details underlying type VII secretion are largely unknown, due to a lack of structural information. Here, we report the molecular architecture of the ESX-5 membrane complex from Mycobacterium xenopi determined at 13 angstrom resolution by electron microscopy. The four core proteins of the ESX-5 complex (EccB(5), EccC(5), EccD(5) and EccE(5)) assemble with equimolar stoichiometry into an oligomeric assembly that displays six-fold symmetry. This membrane-associated complex seems to be embedded exclusively in the inner membrane, which indicates that additional components are required to translocate substrates across the mycobacterial outer membrane. Furthermore, the extended cytosolic domains of the EccC ATPase, which interact with secretion effectors, are highly flexible, suggesting an as yet unseen mode of substrate interaction. Comparison of our results with known structures of other bacterial secretion systems demonstrates that the architecture of type VII secretion system is fundamentally different, suggesting an alternative secretion mechanism.