Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency
Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency
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DOI：
10.1111/mmi.14314
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发表时间：
2019-09-01
影响因子：
3.6
通讯作者：
Helmann, John D.
中科院分区：
文献类型：
--
作者：
Chandrangsu, Pete;Huang, Xiaojuan;Helmann, John D.
细菌严格调节细胞内锌水平，以确保足够的锌来支持基本功能，同时防止毒性。细菌对锌限制的反应包括属于G3E GTPases家族COG0523亚家族1的推定锌金属伴侣的表达。然而，这些伴侣蛋白服务的客户蛋白和代谢过程尚不清楚。在这里，我们证明了枯草芽孢杆菌YciC锌金属伴侣蛋白（这里为ZTP激活的GTPase A更名为ZagA）在锌限制条件下支持叶酸的新生物合成，并直接与锌依赖性GTP环水解酶IA FolE （GCYH-IA）相互作用。此外，我们确定了警报酮ZTP，一种修饰的嘌呤生物合成中间体，在锌限制反应中的作用。ZTP是细菌中10-甲酰基四氢叶酸（10f-THF）缺乏的信号，当FolE开始失效时，ZTP会短暂积累，刺激ZagA和FolE之间的相互作用，从而帮助维持叶酸合成，尽管锌的可用性下降。
Bacteria tightly regulate intracellular zinc levels to ensure sufficient zinc to support essential functions, while preventing toxicity. The bacterial response to zinc limitation includes the expression of putative zinc metallochaperones belonging to subfamily 1 of the COG0523 family of G3E GTPases. However, the client proteins and the metabolic processes served by these chaperones are unclear. Here, we demonstrate that the Bacillus subtilis YciC zinc metallochaperone (here renamed ZagA for ZTP activated GTPase A) supports de novo folate biosynthesis under conditions of zinc limitation, and interacts directly with the zinc-dependent GTP cyclohydrolase IA, FolE (GCYH-IA). Furthermore, we identify a role for the alarmone ZTP, a modified purine biosynthesis intermediate, in the response to zinc limitation. ZTP, a signal of 10-formyl-tetrahydrofolate (10f-THF) deficiency in bacteria, transiently accumulates as FolE begins to fail, stimulates the interaction between ZagA and FolE, and thereby helps to sustain folate synthesis despite declining zinc availability.