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Coordination of bacterial proteome with metabolism by cyclic AMP signalling

机译:细菌蛋白质组与代谢的循环AMP信号协调

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The cyclic AMP (cAMP)-dependent catabolite repression effect in EschericMa coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, theexpression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.
机译:大肠杆菌中依赖环AMP(cAMP)的分解代谢物阻遏作用是生物学研究最深入的调控过程之一。但是,cAMP信号传导的生理功能及其分子触发机制仍然难以捉摸。在这里,我们使用定量的生理学方法来显示cAMP信号紧密结合生物合成和核糖体蛋白分解代谢蛋白的表达,根据指数增长过程中的细胞代谢需要。碳分解代谢基因的表达随着碳流入的限制而随着生长速率的降低线性增加,但随着氮或硫流入的限制而随着生长速率的降低线性降低。相反,生物合成基因的表达与分解代谢基因表现出相反的线性生长速率依赖性。粗粒度数学模型为理解和预测基因表达对分解代谢和合成代谢限制的响应提供了定量框架。提出并验证了一种以代谢前体抑制cAMP信号为特征的积分反馈控制方案。这些结果揭示了依赖cAMP的分解代谢物阻抑的关键生理作用:确保蛋白质组学资源根据不同营养环境的需要用于不同的代谢领域。我们的发现强调了定量生理学在揭示复杂分子信号网络潜在功能方面的力量。

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  • 来源
    《Nature》 |2013年第7462期|301-306|共6页
  • 作者单位

    Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA,Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA;

    Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA,Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA;

    Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA,Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92093-0374 USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA;

    Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA;

    State Key Laboratory of Protein and Plant Gene Research,College of Life Sciences, Peking University, Beijing 100871, China;

    Department of Physics and Center for Synthetic Microbiology, University of Marburg, 35032 Marburg, Germany;

    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA;

    Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA,Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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