Higher-Order Structure in Bacterial VapBC Toxin-Antitoxin Complexes
Higher-Order Structure in Bacterial VapBC Toxin-Antitoxin Complexes
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DOI：
10.1007/978-3-319-46503-6_14
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发表时间：
2017-01-01
期刊：
影响因子：
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通讯作者：
Brodersen, Ditlev E.
中科院分区：
文献类型：
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作者：
Bendtsen, Kirstine L.;Brodersen, Ditlev E.
毒素-抗毒素系统广泛存在于细菌界，包括致病性物种，它们通过选择性抑制关键细胞过程（如DNA复制或蛋白质翻译）来快速适应不断变化的环境条件。在正常生长条件下，II型毒素通过与同源抗毒素蛋白的紧密蛋白质-蛋白质相互作用而被抑制。这种毒素-抗毒素复合物结合成更高级的大分子结构，通常是异源四聚体或异源八聚体，暴露抗毒素上的两个DNA结合结构域，其允许通过直接结合启动子DNA来自动调节转录。在这一章中，我们回顾了我们目前对细菌细胞中II型毒素-抗毒素复合物的结构特征的理解，特别强调了在VapBC家族成员中观察到的令人震惊的各种高阶结构。这种结构多样性是一级序列水平保守性差的结果，可能对毒素-抗毒素表达的调节方式具有重要的功能意义。
Toxin-antitoxin systems are widespread in the bacterial kingdom, including in pathogenic species, where they allow rapid adaptation to changing environmental conditions through selective inhibition of key cellular processes, such as DNA replication or protein translation. Under normal growth conditions, type II toxins are inhibited through tight protein-protein interaction with a cognate antitoxin protein. This toxin-antitoxin complex associates into a higher-order macromolecular structure, typically heterotetrameric or heterooctameric, exposing two DNA binding domains on the antitoxin that allow auto-regulation of transcription by direct binding to promoter DNA. In this chapter, we review our current understanding of the structural characteristics of type II toxin-antitoxin complexes in bacterial cells, with a special emphasis on the staggering variety of higher-order architecture observed among members of the VapBC family. This structural variety is a result of poor conservation at the primary sequence level and likely to have significant and functional implications on the way toxin-antitoxin expression is regulated.