Pseudomonas aeruginosa antitoxin HigA functions as a diverse regulatory factor by recognizing specific pseudopalindromic DNA motifs.
Pseudomonas aeruginosa antitoxin HigA functions as a diverse regulatory factor by recognizing specific pseudopalindromic DNA motifs.
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DOI：
10.1111/1462-2920.15365
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发表时间：
2020-12
影响因子：
5.1
通讯作者：
Ying-Jie Song;G. Luo;Yi-Bo Zhu;Tao Li;Chang-Cheng Li;Lihui He;N. Zhao;Chang Zhao;Jing Yang-Jing-Ya
中科院分区：
文献类型：
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作者：
Ying-Jie Song;G. Luo;Yi-Bo Zhu;Tao Li;Chang-Cheng Li;Lihui He;N. Zhao;Chang Zhao;Jing Yang-Jing-Ya
II型毒素-抗毒素（TA）系统在原核生物中调节许多基本的细胞过程。最近的研究表明，某些II型抗毒素除了中和毒素活性外，还可以转录调节其他基因。本文研究了铜绿假单胞菌ⅱ型TA抗毒素PaHigA的多种转录抑制特性。生化和功能分析表明，PaHigA识别可变假乳病DNA序列，并抑制多个基因的表达。此外，我们还展示了apo-PaHigA、PaHigA-PhigBA和PaHigA-Ppa2440复合物的高分辨率结构，描述了HTH结构域的重排如何解释HigA同源物之间不同的dna结合模式。此外，我们证明了PaHigA的n端环运动与其载脂蛋白和dna结合状态相关，反映了调节HigA抗毒素功能的开关机制。总的来说，这项工作扩展了我们对PaHigB/HigA系统如何调节多种代谢途径以平衡铜绿假单胞菌的生长和应激反应的理解，并可以指导进一步开发以抗ta为导向的病原体治疗策略。这篇文章受版权保护。版权所有。
Type II toxin-antitoxin (TA) systems modulate many essential cellular processes in prokaryotic organisms. Recent studies indicate certain type II antitoxins also transcriptionally regulate other genes, besides neutralizing toxin activity. Herein, we investigated the diverse transcriptional repression properties of type II TA antitoxin PaHigA from Pseudomonas aeruginosa. Biochemical and functional analyses showed that PaHigA recognized variable pseudopalindromic DNA sequences and repressed expression of multiple genes. Furthermore, we presented high resolution structures of apo-PaHigA, PaHigA-PhigBA and PaHigA-Ppa2440 complex, describing how the rearrangements of the HTH domain accounted for the different DNA-binding patterns among HigA homologs. Moreover, we demonstrated that the N-terminal loop motion of PaHigA was associated with its apo and DNA-bound states, reflecting a switch mechanism regulating HigA antitoxin function. Collectively, this work extends our understanding of how the PaHigB/HigA system regulates multiple metabolic pathways to balance the growth and stress response in P. aeruginosa and could guide further development of anti-TA oriented strategies for pathogen treatment. This article is protected by copyright. All rights reserved.