Near-critical behavior of aminoacyl-tRNA pools in E-coli at rate-limiting supply of amino acids

Near-critical behavior of aminoacyl-tRNA pools in E-coli at rate-limiting supply of amino acids
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DOI:
10.1529/biophysj.104.051383
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发表时间:
2005-01-01
影响因子:
3.4
通讯作者:
Ehrenberg, M
Ehrenberg, M
中科院分区:
生物学3区
文献类型:
--
作者:
Elf, J;Ehrenberg, M

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蛋白质合成中不同氨基酸的消耗速率通常与翻译核糖体上密码子使用频率决定的系数化学计量耦合。我们表明,当两个或更多个氨基酸的合成速率限制蛋白质合成,并完全匹配其耦合的消耗率翻译核糖体,氨酰-tRNA的池在三元复合物与延伸因子Tu和GTP是过敏的变化的氨基酸供应率。这种高灵敏度使得宏观分析不确定,因为它伴随着三元复合物的拷贝数的几乎自由的和非线性相关的扩散。这种接近临界的行为与大肠杆菌细胞在缺乏氨基酸的培养基中的平衡生长和大肠杆菌的适应有关。从含氨基酸的生长培养基下调至缺乏氨基酸的生长培养基后的大肠杆菌细胞。利用理论结果讨论了多氨基酸限制条件下氨基酸合成的转录调控、E.大肠杆菌细胞后,营养下调,并提出了一个强大的机制,调节RelA依赖的合成的全球效应分子ppGpp。
The rates of consumption of different amino acids in protein synthesis are in general stoichiometrically coupled with coefficients determined by codon usage frequencies on translating ribosomes. We show that when the rates of synthesis of two or more amino acids are limiting for protein synthesis and exactly matching their coupled rates of consumption on translating ribosomes, the pools of aminoacyl-tRNAs in ternary complex with elongation factor Tu and GTP are hypersensitive to a variation in the rate of amino acid supply. This high sensitivity makes a macroscopic analysis inconclusive, because it is accompanied by almost free and anticorrelated diffusion in copy numbers of ternary complexes. This near-critical behavior is relevant for balanced growth of Escherichia coli cells in media that lack amino acids and for adaptation of E. coli cells after downshifts from amino-acid-containing to amino-acid-lacking growth media. The theoretical results are used to discuss transcriptional control of amino acid synthesis during multiple amino acid limitation, the recovery of E. coli cells after nutritional downshifts and to propose a robust mechanism for the regulation of RelA-dependent synthesis of the global effector molecule ppGpp.