Structural insights into chaperone addiction of toxin-antitoxin systems
Structural insights into chaperone addiction of toxin-antitoxin systems
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DOI：
10.1038/s41467-019-08747-4
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发表时间：
2019-02-15
影响因子：
16.6
通讯作者：
Mourey, Lionel
中科院分区：
文献类型：
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作者：
Guillet, Valerie;Bordes, Patricia;Mourey, Lionel
SecB伴侣通过结合未折叠的蛋白质和SecA马达来帮助蛋白质输出。某些SecB同源物也可以控制毒素-抗毒素（TA）系统，已知该系统在应激反应中调节细菌生长。在这种ta伴侣（TAC）系统中，SecB协助折叠并防止抗毒素降解，从而促进毒素抑制。伴侣依赖是由被称为伴侣依赖（ChAD）序列的抗毒素c端延伸所赋予的，这使得抗毒素容易聚集并阻止毒素抑制。利用结核分枝杆菌的TAC，我们提出了一个与结核菌ChAD肽结合的secb样伴侣蛋白的结构。与SecB-SecA或secb -前蛋白复合物相比，我们发现了结合界面的差异，并表明抗毒素在与伴侣蛋白结合时可以达到功能形式。这项工作揭示了伴侣蛋白如何使用离散的表面结合区域来容纳不同的客户或合作伙伴，从而扩展它们的底物库和功能。
SecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition. Chaperone dependency is conferred by a C-terminal extension in the antitoxin known as chaperone addiction (ChAD) sequence, which makes the antitoxin aggregation-prone and prevents toxin inhibition. Using TAC of Mycobacterium tuberculosis, we present the structure of a SecB-like chaperone bound to its ChAD peptide. We find differences in the binding interfaces when compared to SecB-SecA or SecB-preprotein complexes, and show that the antitoxin can reach a functional form while bound to the chaperone. This work reveals how chaperones can use discrete surface binding regions to accommodate different clients or partners and thereby expand their substrate repertoire and functions.