The crystal structure of the intact E. coli RelBE toxin-antitoxin complex provides the structural basis for conditional cooperativity.
The crystal structure of the intact E. coli RelBE toxin-antitoxin complex provides the structural basis for conditional cooperativity.
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DOI：
10.1016/j.str.2012.08.017
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发表时间：
2012-10-10
期刊：
影响因子：
--
通讯作者：
Brodersen DE
中科院分区：
文献类型：
--
作者：
Bøggild A;Sofos N;Andersen KR;Feddersen A;Easter AD;Passmore LA;Brodersen DE
细菌的relBE位点编码毒素-抗毒素复合物，其中毒素RelE能够在核糖体a位点共翻译切割mRNA。抗毒素RelB既能结合也能抑制RelE，并通过RelE控制的算子结合和条件协同性来调节转录。在这里，我们以2.8 Å的分辨率展示了完整的大肠杆菌RelB2E2复合体的晶体结构，包括RelB抑制的RelE和结合DNA的RelB二聚化结构域。RelE和RelB结合成v形异四聚物，在顶端有带-螺旋-螺旋（RHH）二聚化结构域。我们的结构支持relO与两个相邻的RelB2E异源三聚体最佳结合的模型，而与两个RelB2E2异源四聚体的同时结合不兼容。研究结果为在分子水平上理解条件协同性模型提供了坚实的基础。大肠杆菌RelB2E2复合体具有开放的v形结构►分离的RelB2E2构象灵活►该结构与相邻结合在DNA上的两个拷贝不兼容►该结构提示了条件协同作用的模型细菌使用“自我中毒”来下调细胞过程并适应不断变化的环境。它们使用的毒素是通过与抗毒素紧密结合来调节的，Bøggild等人在这种微妙的调节机制中展示了一个关键中间体的结构。
The bacterial relBE locus encodes a toxin-antitoxin complex in which the toxin, RelE, is capable of cleaving mRNA in the ribosomal A site cotranslationally. The antitoxin, RelB, both binds and inhibits RelE, and regulates transcription through operator binding and conditional cooperativity controlled by RelE. Here, we present the crystal structure of the intact Escherichia coli RelB2E2 complex at 2.8 Å resolution, comprising both the RelB-inhibited RelE and the RelB dimerization domain that binds DNA. RelE and RelB associate into a V-shaped heterotetrameric complex with the ribbon-helix-helix (RHH) dimerization domain at the apex. Our structure supports a model in which relO is optimally bound by two adjacent RelB2E heterotrimeric units, and is not compatible with concomitant binding of two RelB2E2 heterotetramers. The results thus provide a firm basis for understanding the model of conditional cooperativity at the molecular level. ► The E. coli RelB2E2 complex has an open V-shaped structure ► Isolated RelE is conformationally flexible ► The structure is not compatible with two copies binding adjacently on DNA ► The structure suggests a model for conditional cooperativity Bacteria use "self-poisoning" to downregulate cellular processes and to adapt to changing environments. The toxins they use are regulated through tight binding to antitoxins, and Bøggild et al. present the structure of a key intermediate in this subtle regulation mechanism.
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