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 tRNAGlu and tRNAGln. In contrast, in the evolved 20-synthetase systems with GlnRS, the 'discriminating' GluRS aminoacylates only tRNAGlu. Here we report the 2.4 Å resolution crystal structure of a 'discriminating' GluRS · tRNAGlu complex from Thermus thermophilus. The GluRS recognizes the tRNAGlu anticodon bases via two α-helical domains, maintaining the base stacking. We show that the discrimination between the Glu and Gln anticodons (34YUC36 and 34YUG36, respectively) is achieved by a single aginine residue (Arg 358). The mutation of Arg 358 to Gln resulted in a GluRS that does not discriminate between the Glu and Gln anticodons. Tiffs change mimics the reverse course of GluRS evolution from anticodon 'non-discriminating' to 'discriminating'.
All Science Journal Classification (ASJC) codes
- Structural Biology