期刊
ACS INFECTIOUS DISEASES
卷 6, 期 7, 页码 1783-1795出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.0c00048
关键词
tuberculosis; Mycobacterium tuberculosis; TA system; conformational opening MazEF
资金
- National Natural Science Foundation of China [31870782]
- Natural Science Foundation of Guangdong province [2018A030313313, 2017A030310190]
- Fundamental Research Funds for the Central Universities [19lgzd34]
Toxin-antitoxin (TA) systems, which regulate many Apo important cellular processes, are abundantly present in prokaryotic organisms. MazEF is a common type of TA system implicated in the formation of persisters cells of the pathogen Mycobacterium tuberculosis, which contains 10 such systems. However, the exact function and inhibition mode of each MazF protein are not quite understood. Here, we report four high-resolution crystal structures of MazF-mt1 in various forms, including one in complex with MazE-mt1. The toxin displayed two unique interlocked loops that allow the formation of a tight dimer. These loops would open upon interacting with the MazE-mt1 antitoxin mediated by the last two helices of MazE-mt1. With our structure-based design, a mutant that could bind to the antitoxin with an enhanced affinity was produced. Combined crystallographic and biochemical studies further revealed that the binding affinity of MazE-mt1 to MazF-mt1 was mainly attributed to its alpha 3 helical region, while the terminal helix eta 1 contributes very little or even negatively to the association of the pair, in stark contrast to the MazEF-mt9 system. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE/F-mt1 TA pair, which may reflect the functional differences between different TA systems.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据