Role of the 2′, 3′-Isomerization of Aminoacyl-tRNA during Ribosomal Protein Synthesis

Abstract

The structure of aminoacyl-tRNA is not yet established. Moreover, changes of tRNA conformation were suggested to take place after the attachment of the amino acid to the tRNA during the aminoacylation reaction (Potts et al. 1977) and because of codon-dependent binding of aminoacyl-tRNA to ribosomes (Schwarz et al. 1976). Apart from these suggested changes in the tertiary structure during the functional cycle of aminoacyl-tRNA, an obvious structural transformation can occur on the 3′ terminal of the molecule to which the amino acid is attached. The presence of a vicinal cis-diol function on the 3′-terminal A allows a migration of the aminoacyl residue between the 2′- and the 3′-OH groups (Fig. 1). The rate of this isomerization has not yet been determined. An estimate, based on experiments with model substances, suggests that the halftime for isomerization of an average aminoacyl-tRNA in neutral buffered medium at 37°C is about 1.8 × 10⁻⁴ seconds (Griffin et al. 1966). Little attention has been paid to the possible significance of the existence of the isomers, i.e., 2′-aminoacyl-tRNA and 3′-aminoacyl-tRNA, in the elucidation of the mechanism of protein biosynthesis.

In recent years aminoacyl-tRNA species have become available in which the aminoacyl migration can be prevented by a modification of the 3′-terminal A residue. Thus, if the amino acid is linked to a hydroxyl group in which a vicinal cis hydroxyl is missing or to an amino group via an amide bond (Fig. 2), a migration of the amino acid cannot take place. Such tRNA species with...