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SLAC National Accelerator Laboratory

The Structure and Dynamics of Eukaryotic Glutaminyl-tRNA Synthetase
May 2013 SSRL Science Summary by Lori Ann White, SLAC Office of Communications

Full-length Gln4 shown bound to tRNAgln

Aminoacyl-tRNA synthetases are required in all three domains of life to add the correct amino acid to its cognate tRNA, an essential step in protein synthesis. Despite their importance, no structure had been reported for any full-length eukaryotic, glutaminyl-tRNA synthetase (GlnRS), although structural data for two prokaryotic GlnRS species exists. A group led by Edward Snell of the Hauptman-Woodward Medical Research Institute has recently used data from SSRL to develop a model of the full-length enzyme in solution. Using crystallographic structures and homology with known complexes, they also modeled the full-length enzyme bound to tRNAgln.

Two basic pathways exist for aminoacylation of glutamine: In eukaryotes and some bacteria, the glutaminyl-tRNA synthetase (GlnRS) binds to tRNAgln, glutamine and ATP and first forms a glutaminyl adenylate molecule that is then covalently attached to the 3’-end of tRNAgln with the release of AMP, while in most bacteria and all archaea a non-discriminating glutamyl-tRNA synthetase (GluRS) attaches glutamic acid to both tRNAglu and tRNAgln. The misacylated glu-tRNAgln is then converted to gln-tRNAgln by the GatCAB amidotransferase enzyme in bacteria and some archaea, or by the GatDE amidotransferases in other archaea.

Using remotely collected macromolecular crystallography data from SSRL, Snell's group first determined the structure of the N-terminal domain (NTD) for the specific glutaminyl-tRNA synthetase (ScGlnRS) found in the eukaryote Saccharomyces cerevisiae, revealing that it has an extraordinary structural resemblance to the region of the B subunit of the GatCAB amidotransferase that binds to tRNAgln. Using SSRL Beam Line 11-1, Snell's group next determined the crystal structure of the C-terminal domain (CTD) of ScGlnRS. This structure, the structure of the NTD and small angle x-ray scattering (SAXS) data measured at SSRL Beam Line 4-2 enabled Snell's group to create their model of the full-length enzyme in solution. This model, combined with the model of the full-length enzyme bound to tRNAgln, suggests that C-terminal domain-binding to tRNA results in a large conformational reorientation of the N-terminal domain, enabling interactions between it and the tRNA. The combination of crystallographic and solution studies enabled by SSRL facilities has yielded fundamental new insights into the structural rearrangements occurring in eukaryotic GlnRS-tRNAgln complex formation.


Primary Citations

T. D. Grant, J. R. Luft, J. R. Wolfley, M. E. Snell, H. Tsuruta, S. Corretore, E. Quartley, E. M. Phizicky, E. J. Grayhack and E. H. Snell, "The Structure of Yeast Glutaminyl-tRNA Synthetase and Modeling of Its Interaction with tRNA", J. Mol. Biol. (2013) doi: 10.1016/j.jmb.2013.03.043

Related Links


Edward Snell, SUNY Buffalo / Hauptman-Woodward Medical Research Institute

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