Near-critical behavior of aminoacyl-tRNA pools in E. coli at rate-limiting supply of amino acids.
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.
Elf
Johan
J
Department of Cell & Molecular Biology, BMC, Uppsala University, S-751 24 Uppsala, Sweden.
Ehrenberg
Måns
M
D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D001703:Biophysics / Q000379:methods*; D003062:Codon; D003198:Computer Simulation; D003470:Culture Media / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000737:chemistry; D007700:Kinetics; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D016328:NF-kappa B / Q000378:metabolism; D010444:Peptide Elongation Factor Tu / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry; D012680:Sensitivity and Specificity; D013997:Time Factors; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D046249:Transfer RNA Aminoacylation
D000596:Amino Acids; D003062:Codon; D003470:Culture Media; D016328:NF-kappa B; D011506:Proteins; D051996:Transcription Factor RelA; D006160:Guanosine Triphosphate; D010444:Peptide Elongation Factor Tu