An endogenous protein inhibitor, YjhX (TopAI), for topoisomerase I from Escherichia coli.
An endogenous protein inhibitor, YjhX (TopAI), for topoisomerase I from Escherichia coli.
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DOI：
10.1093/nar/gkv1197
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发表时间：
2015-12-02
影响因子：
14.9
通讯作者：
Inouye M
中科院分区：
文献类型：
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作者：
Yamaguchi Y;Inouye M
几乎所有自由生活的细菌的基因组上都含有毒素-抗毒素(TA)系统，并且毒素的靶标非常不同。在这里，我们在大肠杆菌中发现了一个新的、以前未知的TA系统，命名为yjhX-yjhQ。YjhX(85个氨基酸残基)的诱导会导致细胞生长停滞，导致细胞死亡，而YjhQ(181个残基)的共同诱导会使细胞恢复生长。YjhX的主要细胞靶点是拓扑异构酶I(TopA)，抑制DNA复制和RNA合成。值得注意的是，YjhX与TA系统的任何其他毒素没有同源性。YjhX在N-末端的可溶性蛋白S(PrS)中得到了较好的表达。在没有DNA的情况下，PrS-YjhX与TopA(TopA67)的N-末端区域发生特异的相互作用，而在DNA存在的情况下不能与完整的TopA结合。值得注意的是，YjhX不直接与DNA和RNA相互作用。在体外，YjhX仅抑制拓扑异构酶I，而不抑制拓扑异构酶III和IV。因此，yjhX被重新命名为TopA抑制基因(topAI基因)。TopAI是第一个针对拓扑异构酶I的内源性蛋白抑制剂。
Almost all free-living bacteria contain toxin-antitoxin (TA) systems on their genomes and the targets of toxins are highly diverse. Here, we found a novel, previously unidentified TA system in Escherichia coli named yjhX-yjhQ. Induction of YjhX (85 amino acid residues) causes cell-growth arrest resulting in cell death, while YjhQ (181 residues) co-induction resumes cell growth. The primary cellular target of YjhX was found to be topoisomerase I (TopA), inhibiting both DNA replication and RNA synthesis. Notably, YjhX has no homology to any other toxins of the TA systems. YjhX was expressed well with an N-terminal protein S (PrS) tag in soluble forms. PrS-YjhX specifically interacts with the N-terminal region of TopA (TopA67) but not full-TopA in the absence of plasmid DNA, while PrS-YjhX binds to full-TopA in the presence of DNA. Notably, YjhX does not directly interact with DNA and RNA. YjhX inhibits only topoisomerase I but not topoisomerase III and IV in vitro. Hence, yjhX is renamed as the gene for the TopA inhibitor (the topAI gene). TopAI is the first endogenous protein inhibitor specific for topoisomerase I.