Structural basis for anticodon recognition by discriminating glutamyl-tRNA synthetase

Glutamyl-tRNA synthetases (GluRSs) are divided into two distinct types, with regard to the presence or absence of glutaminyl-tRNA synthetase (GlnRS) in the genetic translation systems. In the original 19-synthetase systems lacking GlnRS, the 'non-discriminating' GluRS glutamylates both tRNA Glu and tRNA Gln . In contrast, in the evolved 20-synthetase systems with GlnRS, the 'discriminating' GluRS aminoacylates only tRNA Glu . Here we report the 2.4 Å resolution crystal structure of a 'discriminating' GluRS·tRNA Glu complex from Thermus thermophilus . The GluRS recognizes the tRNA Glu anticodon bases via two α-helical domains, maintaining the base stacking. We show that the discrimination between the Glu and Gln anticodons ( 34 YUC 36 and 34 YUG 36 , respectively) is achieved by a single arginine residue (Arg 358). The mutation of Arg 358 to Gln resulted in a GluRS that does not discriminate between the Glu and Gln anticodons. This change mimics the reverse course of GluRS evolution from anticodon 'non-dicsriminating' to 'discriminating'.