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The physiological target for LeuRS translational quality control is norvaline

Cvetešić, Nevena; Palencia, Andres; Halasz, Ivan; Cusack, Stephen; Gruić-Sovulj, Ita (2014) The physiological target for LeuRS translational quality control is norvaline. EMBO Journal, 33 (15). pp. 1639-1653. ISSN 0261-4189

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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.

Item Type: Article
Uncontrolled Keywords: editing; isoleucine; leucyl-tRNA synthetase; micro-aerobic growth; norvaline
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Physical Chemistry
Projects:
Project titleProject leaderProject codeProject type
Nekanonske uloge aminoacil-tRNA-sintetazaUNSPECIFIEDIS-09.01/293HRZZ
Depositing User: Ivan Halasz
Date Deposited: 11 Mar 2016 12:36
Last Modified: 05 May 2017 08:54
URI: http://fulir.irb.hr/id/eprint/2575
DOI: 10.15252/embj.201488199

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