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EMBO J. 2014 Aug 1;33(15):1639-53. doi: 10.15252/embj.201488199. Epub 2014 Jun 16.

The physiological target for LeuRS translational quality control is norvaline.

Author information

1
Department of Chemistry, Faculty of Science University of Zagreb, Zagreb, Croatia.
2
European Molecular Biology Laboratory, Grenoble Outstation and Unit of Virus Host-Cell Interactions, University of Grenoble Alpes-EMBL-CNRS UMI 3265, France.
3
Ruder Boskovic Institute, Zagreb, Croatia.
4
Department of Chemistry, Faculty of Science University of Zagreb, Zagreb, Croatia gruic@chem.pmf.hr.

Abstract

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 tRNAs. 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.

KEYWORDS:

editing; isoleucine; leucyl‐tRNA synthetase; micro‐aerobic growth; norvaline

PMID:
24935946
PMCID:
PMC4194098
DOI:
10.15252/embj.201488199
[Indexed for MEDLINE]
Free PMC Article

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