Fic Proteins Inhibit the Activity of Topoisomerase IV by AMPylation in Diverse Bacteria
Fic Proteins Inhibit the Activity of Topoisomerase IV by AMPylation in Diverse Bacteria
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Fic 蛋白通过 AMPylation 在多种细菌中抑制拓扑异构酶 IV 的活性。
DOI：
10.3389/fmicb.2020.02084
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发表时间：
2020-08-26
影响因子：
5.2
通讯作者：
Luo, Zhao-Qing
中科院分区：
文献类型：
--
作者：
Lu, Can-Hua;McCloskey, Alix;Luo, Zhao-Qing
Fic结构域是一个广泛分布的基序，具有HPFx[D/E]GN[G/K]R的保守序列，其中一些通过催化AMP部分从ATP转移到蛋白质底物来调节细胞活性。土壤细菌荧光假单胞菌（Pseudomonasfluorescensstrain）2 P24中的Fic-1等Fic蛋白可通过对DNA促旋酶（GyrB）的亚基B进行腺苷酸化而抑制细菌DNA的复制，但其生物活性和细胞靶位尚不清楚。在此，我们报道了来自菌株2 P24的另一种Fic蛋白Fic-2和Fic-1在Tyr（109）处腺苷酸化拓扑异构酶IV帕雷。我们还检测了来自几种遗传多样性细菌的Fic蛋白，发现来自假结核耶尔森氏菌和金黄色葡萄球菌的Fic蛋白分别为AMPylate帕雷和GrlB，GrlB是革兰氏阳性菌中帕雷的对应物。Fic-1对P.荧光和FicY。pseudotuberculosus抑制拓扑异构酶IV的松弛活性。与帕雷活性的抑制一致，这些Fic蛋白的异位表达引起细胞的表达，类似于典型的parphenotype，其中类核在伸长细胞的中心组装，这一过程伴随着SOS反应的诱导。我们的研究结果表明，来自不同细菌物种的Fic蛋白通过靶向帕雷调节细菌中的染色体分裂和细胞分离。
The Fic (filamentation induced by cyclic AMP) domain is a widely distributed motif with a conserved sequence of HPFx[D/E]GN[G/K]R, some of which regulate cellular activity by catalyzing the transfer of the AMP moiety from ATP to protein substrates. Some Fic proteins, including Fic-1 from the soil bacteriumPseudomonas fluorescensstrain 2P24, have been shown to inhibit bacterial DNA replication by AMPylating the subunit B of DNA gyrase (GyrB), but the biochemical activity and cellular target of most Fic proteins remain unknown. Here, we report that Fic-2, which is another Fic protein from strain 2P24 and Fic-1 AMPylate the topoisomerase IV ParE at Tyr(109). We also examined Fic proteins from several phylogenetically diverse bacteria and found that those fromYersinia pseudotuberculosisandStaphylococcus aureusAMPylate ParE and GrlB, the counterpart of ParE in Gram-positive bacteria, respectively. Modification by Fic-1 ofP. fluorescensand FicY ofY. pseudotuberculosisinhibits the relaxation activity of topoisomerase IV. Consistent with the inhibition of ParE activity, ectopic expression of these Fic proteins causes cell filamentation akin to the canonicalparphenotype in which nucleoids are assembled in the center of elongated cells, a process accompanied by the induction of the SOS response. Our results establish that Fic proteins from diverse bacterial species regulate chromosome division and cell separation in bacteria by targeting ParE.