Elongation factor Tu.guanosine 3'-diphosphate 5'-diphosphate complex increases the fidelity of proofreading in protein biosynthesis: mechanism for reducing translational errors introduced by amino acid starvation.
Complexes of elongation factor Tu (EF-Tu) with guanosine 3'-diphosphate 5'-diphosphate (ppGpp) bind to ribosomes where they slow the incorporation of aminoacyl-tRNAs into protein by inhibiting both the binding of aminoacyl-tRNA.EF-Tu.GTP ternary complexes and the formation of peptide bonds. The latter action increases the time available for aminoacyl-tRNA rejection by the ribosome and, therefore, increases the effectiveness of proofreading. Synthesis of ppGpp and the formation of EF-Tu.ppGpp occur in vivo in response to amino acid starvation. Our finding, therefore, suggests an explanation for the otherwise puzzling observation that amino acid starvation has, at most, a moderate effect on the fidelity of protein synthesis in wild-type Escherichia coli. We suggest that an EF-Tu.ppGpp-induced increase in the effectiveness of proofreading buffers the overall translational fidelity of these cells against amino acid starvation-induced errors in initial selection of aminoacyl-tRNA ternary complexes.
D004926:Escherichia coli; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D014176:Protein Biosynthesis; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
D006150:Guanine Nucleotides; D046911:Macromolecular Substances; D012346:RNA, Transfer, Amino Acyl; D006153:Guanosine Diphosphate; D006159:Guanosine Tetraphosphate; D010444:Peptide Elongation Factor Tu