定量绝对蛋白质合成率揭示了细胞资源分配的基本原理。
Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources.
机构信息
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute of Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
California Institute of Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
出版信息
Cell. 2014 Apr 24;157(3):624-35. doi: 10.1016/j.cell.2014.02.033.
Quantitative views of cellular functions require precise measures of rates of biomolecule production, especially proteins-the direct effectors of biological processes. Here, we present a genome-wide approach, based on ribosome profiling, for measuring absolute protein synthesis rates. The resultant E. coli data set transforms our understanding of the extent to which protein synthesis is precisely controlled to optimize function and efficiency. Members of multiprotein complexes are made in precise proportion to their stoichiometry, whereas components of functional modules are produced differentially according to their hierarchical role. Estimates of absolute protein abundance also reveal principles for optimizing design. These include how the level of different types of transcription factors is optimized for rapid response and how a metabolic pathway (methionine biosynthesis) balances production cost with activity requirements. Our studies reveal how general principles, important both for understanding natural systems and for synthesizing new ones, emerge from quantitative analyses of protein synthesis.
细胞功能的定量观点需要精确测量生物分子（尤其是蛋白质）的产生速率，因为蛋白质是生物过程的直接效应物。在这里，我们提出了一种基于核糖体谱分析的全基因组方法来测量绝对蛋白质合成速率。由此产生的大肠杆菌数据集改变了我们对蛋白质合成受到精确控制以优化功能和效率的程度的理解。多蛋白复合物的成员按其化学计量比精确制造，而功能模块的组件则根据其层次角色差异产生。绝对蛋白质丰度的估计还揭示了优化设计的原则。这些原则包括不同类型转录因子的水平如何针对快速响应进行优化，以及代谢途径（甲硫氨酸生物合成）如何平衡生产成本与活性要求。我们的研究揭示了如何从蛋白质合成的定量分析中得出对理解自然系统和合成新系统都很重要的一般原则。
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