Structural Bases of Transfer RNA-Dependent Amino Acid Recognition and Activation by Glutamyl-tRNA Synthetase

SummaryGlutamyl-tRNA synthetase (GluRS) is one of the aminoacyl-tRNA synthetases that require the cognate tRNA for specific amino acid recognition and activation. We analyzed the role of tRNA in amino acid recognition by crystallography. In the GluRS
• tRNAGlu
• Glu structure, GluRS and tRNAGlu collaborate to form a highly complementary L-glutamate-binding site. This collaborative site is functional, as it is formed in the same manner in pretransition-state mimic, GluRS
• tRNAGlu
• ATP
• Eol (a glutamate analog), and posttransition-state mimic, GluRS
• tRNAGlu
• ESA (a glutamyl-adenylate analog) structures. In contrast, in the GluRS
• Glu structure, only GluRS forms the amino acid-binding site, which is defective and accounts for the binding of incorrect amino acids, such as D-glutamate and L-glutamine. Therefore, tRNAGlu is essential for formation of the completely functional binding site for L-glutamate. These structures, together with our previously described structures, reveal that tRNA plays a crucial role in accurate positioning of both L-glutamate and ATP, thus driving the amino acid activation.