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The physiological target for Leu RS translational quality control is norvaline
Author(s) -
Cvetesic Nevena,
Palencia Andrés,
Halasz Ivan,
Cusack Stephen,
GruicSovulj Ita
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201488199
Subject(s) - norvaline , biology , isoleucine , amino acid , transfer rna , escherichia coli , biochemistry , aminoacyl trna synthetase , amino acyl trna synthetases , rna editing , translation (biology) , protein biosynthesis , leucine , rna , messenger rna , gene
The fidelity of protein synthesis depends on the capacity of aminoacyl‐ tRNA synthetases (AARSs) to couple only cognate amino acid‐ tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNA s. Here, we show that the editing activity of Escherichia coli leucyl‐ tRNA synthetase (EcLeuRS) is not required to prevent incorrect isoleucine incorporation. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis‐incorporation of the non‐standard amino acid norvaline. This conclusion follows from a reassessment of the discriminatory power of LeuRS against isoleucine and the demonstration that a LeuRS editing‐deficient E. coli strain grows normally in high concentrations of isoleucine but not under oxygen deprivation conditions when norvaline accumulates to substantial levels. Thus, AARS‐based translational quality control is a key feature for bacterial adaptive response to oxygen deprivation. The non‐essential role for editing under normal bacterial growth has important implications for the development of resistance to antimicrobial agents targeting the LeuRS editing site.