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The ATPases of the mycobacterial type VII secretion system: Structural and mechanistic insights into secretion.
Progress in Biophysics and Molecular Biology ( IF 3.2 ) Pub Date : 2019-11-22 , DOI: 10.1016/j.pbiomolbio.2019.11.008
Thomas D Crosskey 1 , Katherine S H Beckham 1 , Matthias Wilmanns 2
Affiliation  

Tuberculosis (TB) remains the foremost cause of death by infectious disease and is propagated by the pathogen Mycobacterium tuberculosis (Mtb). The virulence associated with Mtb is mediated by proteins secreted into host cells by the type VII secretion system (T7SS), making this system a candidate for future drug and vaccine development. However, while many of the components involved in the T7SS have been identified, the mechanism of translocation across both the inner and outer mycobacterial membranes remains largely unexplained. Key to the translocation of proteins across the membrane is the activity of conserved AAA+ ATPases EccA and EccC, which are explored in this review. Although the T7SS does not appear homologous to other known bacterial secretion systems, many of those require ATPase activity during different phases of protein translocation. Thus, exploring the roles of ATPases in multiple secretion systems may provide insights into the T7SS. Targeting bacterial virulence factors such as secretion systems is becoming an increasingly explored area of research, and here we review how such strategies could be applied to the T7SS.



中文翻译:

VII型分枝杆菌分泌系统的ATPases:对分泌的结构和机理的认识。

结核病(TB)仍然是传染病致死的首要原因,并由病原体结核分枝杆菌传播(MTB)。与mtb相关的毒力是由VII型分泌系统(T7SS)分泌到宿主细胞中的蛋白质介导的,这使得该系统成为未来药物和疫苗开发的候选者。然而,虽然已经确定了T7SS涉及的许多组件,但在内部和外部分枝杆菌膜上易位的机制仍然无法解释。蛋白质跨膜转运的关键是保守的AAA + ATPases EccA和EccC的活性,本综述对此进行了探讨。尽管T7SS与其他已知的细菌分泌系统似乎并不同源,但其中许多在蛋白质易位的不同阶段都需要ATPase活性。因此,探索ATP酶在多种分泌系统中的作用可提供对T7SS的了解。

更新日期:2019-11-22
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