Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology
Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology
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DOI：
10.1016/j.celrep.2015.07.056
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发表时间：
2015-09-01
期刊：
影响因子：
8.8
通讯作者：
Dehio, Christoph
中科院分区：
文献类型：
--
作者：
Harms, Alexander;Stanger, Frederic Valentin;Dehio, Christoph
毒素-抗毒素(TA)模块是普遍存在的分子开关，通过释放抑制细胞增殖的毒素来控制细菌的生长。这些毒素中的大多数会干扰蛋白质的翻译，但越来越多的其他机制暗示了一种尚未完全认识到的多样性。在这里，我们将一组FIC结构域蛋白定性为保守且丰富的TA模块FicTA家族的毒素，并揭示它们通过暂停控制细胞DNA拓扑而发挥作用。我们发现FicT是腺化DNA旋转酶和拓扑异构酶IV的酶，这两种酶是基本的细菌IIA拓扑异构酶，在它们的ATP结合部位。这种修饰通过阻止这两个靶点的ATPase活性来使其失活，因此，由于细胞DNA的打结、连锁和松弛，导致可逆的生长停滞。我们的结果深入了解了DNA拓扑的调节，并突出了FIC结构域蛋白的显着可塑性。
Toxin-antitoxin (TA) modules are ubiquitous molecular switches controlling bacterial growth via the release of toxins that inhibit cell proliferation. Most of these toxins interfere with protein translation, but a growing variety of other mechanisms hints at a diversity that is not yet fully appreciated. Here, we characterize a group of FIC domain proteins as toxins of the conserved and abundant FicTA family of TA modules, and we reveal that they act by suspending control of cellular DNA topology. We show that FicTs are enzymes that adenylylate DNA gyrase and topoisomerase IV, the essential bacterial type IIA topoisomerases, at their ATP-binding site. This modification inactivates both targets by blocking their ATPase activity, and, consequently, causes reversible growth arrest due to the knotting, catenation, and relaxation of cellular DNA. Our results give insight into the regulation of DNA topology and highlight the remarkable plasticity of FIC domain proteins.