Recognition in the Glutamine tRNA System: from Structure to Function

The ability of aminoacyl-tRNA synthetases (aaRS) to faithfully recognize both their amino acid and tRNA substrates is essential for accurate protein synthesis. This chapter focuses on the recognition of tRNA by Escherichia coli glutaminyl-tRNA synthetase (GlnRS). This system is arguably the best characterized aaRS-tRNA interaction both functionally and structurally, as the first high-resolution crystal structure of a protein-RNA complex was solved for GlnRS:tRNAGln. The chapter summarizes the characteristics of the GlnRS:tRNAGln system that make GlnRS unique among aaRS, as well as those that make the glutamine system an ideal model for the study of protein-RNA interaction, specifically aaRS-tRNA interaction. Together the crystal structure, genetic, and biochemical studies have identified the most important specificity determinants from among the hundreds of contacts between GlnRS and tRNAGln. The chapter also describes several of the more interesting aspects of the GlnRS:tRNAGln system: (1) the close evolutionary relationship between GlnRS and glutamyl-tRNA synthetase (GluRS); (2) GlnRS's relaxed discrimination against noncognate tRNAs coupled with its "overdetermined," tight recognition of its cognate tRNA; and (3) the enzyme mechanism of GlnRS, specifically the structural and functional communication that permits this small monomeric aaRS to recognize tRNA identity elements that are more than 75A apart in uncomplexed tRNA. The information obtained from biophysical techniques (crystallography, fluorescence, and x-ray/neutron scattering) and from genetic and biochemical approaches is combined to yield a coherent and detailed picture of the specific recognition of tRNA by E. coli GlnRS.