Evolution of the bacterial nucleosidase PpnN and its relation to the stringent response

IF 4.1 3区 生物学 Q2 CELL BIOLOGY Microbial Cell Pub Date : 2019-07-16 DOI:10.15698/mic2019.09.692
René L. Bærentsen, D. Brodersen, Y. Zhang
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引用次数: 4

Abstract

In our recent publication (Zhang et al., 2019), we demonstrate an interesting mode of regulation of purine metabolism unique to Proteobacteria. In this microreview, we would like to reflect on the ideas put forward, with special focus on protein domain architecture of the enzyme involved, its orthologues in plants, and the implications of the differential effects observed between binding of the two alarmone molecules, ppGpp (guanosine 3′,5′-bisdiphosphate) and pppGpp (guanosine-5′-triphosphate-3′-diphosphate). In our previous work, we showed that the Escherichia coli nucleotide 5'-monophosphate nucleosidase, PpnN, which is conserved in Proteobacteria, cleaves its preferred substrate, guanosine monophosphate (GMP), at a much higher rate in the presence of both pppGpp and ppGpp (Figure 1A). Structural analysis reveals that binding of pppGpp leads to a conformational change in the protein that exposes its active site, suggesting this is the reason for the observed increase in activity. Finally, point mutation of the alarmone-interacting residues show a defect in binding, resulting in (i) increased basal catalytic activity of PpnN and higher competitive fitness of E. coli in an environment with fluctuating nutrient levels, and (ii) increased bacterial sensitivity towards antibiotics. In contrast, complete loss of the ppnN gene has the inverse effect, i.e. reduced competitive growth and improved antibiotic tolerance. We used these observations to propose a model in which E. coli uses PpnN to balance the need of fitness (fast growth) against tolerance towards antibiotics to improve survival.
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细菌核糖苷酶PpnN的进化及其与严格反应的关系
在我们最近的出版物(Zhang et al.,2019)中,我们展示了变形杆菌特有的嘌呤代谢调控模式。在这篇微综述中,我们想反思所提出的观点,特别关注所涉及的酶的蛋白质结构域结构、其在植物中的同源物,以及观察到的两种鸟嘌呤分子ppGpp(鸟苷3′,5′-二磷酸)和pppGpp(鸟苷5′-三磷酸-3′-二磷酸盐)结合之间的差异效应的含义。在我们之前的工作中,我们发现在变形杆菌中保守的大肠杆菌核苷酸5'-单磷酸核苷酶PpnN在pppGpp和ppGpp存在的情况下,以更高的速率切割其首选底物鸟苷(GMP)(图1A)。结构分析表明,pppGpp的结合导致暴露其活性位点的蛋白质的构象变化,这表明这是观察到的活性增加的原因。最后,alarmone相互作用残基的点突变显示出结合缺陷,导致(i)PpnN的基础催化活性增加,大肠杆菌在营养水平波动的环境中具有更高的竞争适应性,以及(ii)细菌对抗生素的敏感性增加。相反,ppnN基因的完全缺失具有相反的效果,即减少竞争性生长和提高抗生素耐受性。我们利用这些观察结果提出了一个模型,在该模型中,大肠杆菌使用PpnN来平衡适应度(快速生长)的需求和对抗生素的耐受性,以提高生存率。
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来源期刊
Microbial Cell
Microbial Cell Multiple-
CiteScore
6.40
自引率
0.00%
发文量
32
审稿时长
12 weeks
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