Aminoacyl-tRNA Synthetases: Occurrence, Structure, and Function

Translation of the genetic message into proteins implies the precise correspondence between the 64 base triplets and the 20 canonical amino acids. In this process, the tRNAs play a central role by providing the nascent polypeptide with the amino acids by which they are esterified, in response to codons on the mRNA. The pairing of mRNA codon to tRNA anticodon is independent of the nature of the amino acid esterified to the tRNA. Therefore, the accuracy of the tRNA aminoacylation reaction, ensured by the aminoacyl-tRNA synthetases (aaRS), is of first importance in all living cells, since it will govern, to a large extent, the fidelity of the translation process. Much work has been done to understand how aaRS achieve high accuracy of tRNA aminoacylation while maintaining a sufficiently high rate of catalysis, generally in the order of several turnovers per second.. Since the early description of aaRS, most of the studies have focused on the kinetic mechanisms of action of the aaRS. More recently, with the availability of the three-dimensional structure of several tRNAs and synthetases and the possibility of generating variants of these macromolecules, a static picture of their specific interaction at the atomic level has emerged. Two main functions are carried out by an aaRS: the activation of the amino acid and the recognition of the tRNA molecule. In addition, association between protomers must be ensured. The present knowledge indicates that each of these functions is distributed along the aaRS polypeptide through the formation of specialized domains.