Abstract
The homochirality of amino acids is vital for the functioning of the translation apparatus. l-Amino acids predominate in proteins and d-amino acids usually represent diverse regulatory functional physiological roles in both pro- and eukaryotes. Aminoacyl-tRNA-synthetases (aaRSs) ensure activation of proteinogenic or nonproteinogenic amino acids and attach them to cognate or noncognate tRNAs. Although many editing mechanisms by aaRSs have been described, data about the protective role of aaRSs in d-amino acids incorporation remained unknown. Tyrosyl- and alanyl-tRNA-synthetases were represented as distinct members of this enzyme family. To study the potential to bind and edit noncognate substrates, Thermus thermophilus alanyl-tRNA-synthetase (AlaRS) and tyrosyl-tRNA-synthetase were investigated in the context of d-amino acids recognition. Here, we showed that d-alanine was effectively activated by AlaRS and d-Ala-tRNAAla, formed during the erroneous aminoacylation, was edited by AlaRS. On the other hand, it turned out that d-aminoacyl-tRNA-deacylase (DTD), which usually hydrolyzes d-aminoacyl-tRNAs, was inactive against d-Ala-tRNAAla. To support the finding about DTD, computational docking and molecular dynamics simulations were run. Overall, our work illustrates the novel function of the AlaRS editing domain in stereospecificity control during translation together with trans-editing factor DTD. Thus, we propose different evolutionary strategies for the maintenance of chiral selectivity during translation.
Highlights
Homochirality of amino acids is essential for natural protein biosynthesis, and only L-enantiomers are present in proteins
Together with molecular dynamics (MD) simulations and kinetics data, we propose an evolutionary strategy for the chiral selectivity of the translation apparatus
We compared the potency of stereospecificity control in protein biosynthesis by evolutionarily early (AlaRS) and late (TyrRS) representatives of the aaRSs family (Tables 1 and 2; Figure 1)
Summary
The strict chiral prevalence in biological molecules is displayed in every single organism on Earth. In contrast to living species, organic materials in the universe are found in a racemic mixture [1,2]. In this context, an organismindependent mixture of amino acids found in the Murchison meteorite demonstrated that alanine (Ala) and achiral glycine (Gly)––the simplest amino acids––had the highest abundance [3]. The D/L-Ala molar ratio was shown to be almost 50/50 [4]. Homochirality of amino acids is essential for natural protein biosynthesis, and only L-enantiomers are present in proteins. The selectivity of L-amino acids was determined by the stereochemistry of RNA [5]
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