Original scientific paper

https://doi.org/10.5562/cca2173

Lack of Discrimination Against Non-proteinogenic Amino Acid Norvaline by Elongation Factor Tu from Escherichia coli

Nevena Cvetešić ; Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia
Irena Akmačić ; Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia
Ita Gruić-Sovulj ; Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia

Abstract

The GTP-bound form of elongation factor Tu (EF-Tu) brings aminoacylated tRNAs (aa-tRNA)
to the A-site of the ribosome. EF-Tu binds all cognate elongator aa-tRNAs with highly similar affinities,
and its weaker or tighter binding of misacylated tRNAs may discourage their participation in translation.
Norvaline (Nva) is a non-proteinogenic amino acid that is activated and transferred to tRNALeu by leucyltRNA
synthetase (LeuRS). No notable accumulation of Nva-tRNALeu has been observed in vitro, because
of the efficient post-transfer hydrolytic editing activity of LeuRS. However, incorporation of norvaline into
proteins in place of leucine does occur under certain conditions in vivo. Here we show that EF-Tu binds
Nva-tRNALeu and Leu-tRNALeu with similar affinities, and that Nva-tRNALeu and Leu-tRNALeu dissociate
from EF-Tu at comparable rates. The inability of EF-Tu to discriminate against norvaline may have driven
evolution of highly efficient LeuRS editing as the main quality control mechanism against
misincorporation of norvaline into proteins. (doi: 10.5562/cca2173)

Keywords

EF-Tu; norvaline; non-proteinogenic amino acids; aminoacyl-tRNA synthetases; leucyl-tRNA synthetase; mistranslation

Hrčak ID:

101911

URI

https://hrcak.srce.hr/101911

Publication date:

3.5.2013.

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