Glutaminyl-tRNA Synthetase

Glutaminyl-tRNA synthetase (GlnRS) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid glutamine to its cognate tRNA: $ \text{Gln} + \text{tRNA}^\text{Gln} + \text{ATP} \xrightarrow{\text{GlnRS}} \text{Gln-tRNA}^\text{Gln} + \text{AMP} + \text{PP}_i $ As discussed by Hadd and Perona 2014, there is a complex coevolutionary history between glutamyl- and glutaminyl-tRNA synthetases, which comprise subclass Ib (Perona and Hadd. 2012, Gomez et al., 2020). Their diversification occurred after the last universal common ancestor, with bacterial-like forms being characterized by an [$\alpha$-helical anticodon binding domain](/superfamily/class1/Anticodon_binding_domain_EK), and the archaeal and eukaryotic forms possessing a [$\beta$-barrel anticodon binding domain](/superfamily/class1/Anticodon_binding_domain_EQ). While many contemporary systems express both GlnRS and GluRS, their ancestor was most likely a non-discriminating form, which would attach Glu to tRNA$^\text{Gln}$. A second enzymatic step, performed by an amidotransferase, would correct the misacylated tRNA prior to protein synthesis, as it does with [AsxRS](/class2/asp2/) (Lapointe et al. 1986, Raczniak et al. 2001). This non-discriminating enzyme is still found in systems which lack GlnRS, such the archaea, which express [GlxRS-A](/class1/glu2/), as well as certain bacteria which have a non-discriminating variant [GlxRS-B](/class1/glu1/), or a noncognate variant GluGlnRS which attaches Glu to tRNA$^\text{Gln}$ (Salazar et al. 2003, Skouloubris et al. 2003). It is likely that GlnRS originated in the eukaryota, and was later acquired by certain bacteria through horizontal gene transfer (Siatecka et al. 1998). The N-terminal catalytic domain of GlnRS closely resembles that of [GluRS-B](/class1/glu1/) , [GluRS-E](/class1/glu3/), and [GlxRS-A](/class1/glu2/) , constituting subclass Ib (Perona and Hadd 2012, Gomez et al., 2020). Their catalytic domains are characterized by an insertion within CP1, containing a loop flanked by two helices (SC1b IM), which may play a role in acceptor stem recognition (Rath et al. 1998, Nureki et al. 2010). Its $\beta$-barrel anticodon binding domain is located at the C-terminal end (Rould et al. 1991) and is homologous with that of GlxRS-A and GluRS-E. However it is distinct to the bacterial form GluRS-B, which instead has an $\alpha$-helical anticodon binding domain. Members of subclass Ib, alongside [ArgRS](/class1/arg/) and [LysRS-I](/class1/lys/), require the presence of tRNA to catalyze activation of the amino acid substrate (Dubois et al. 2005). In many eukaryotes, the N-terminal contains a helical domain homologous to the Yqey domain found in amidotransferases (Hadd et al. 2014), and is required for the assembly of the MARS complex (Kim et al. 2000). It may also contribute to the enzyme's ability to discriminate against tRNA$^\text{Glu}$ (Hadd et al. 2014).

References

John J. Perona. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 9: Glutaminyl-tRNA Synthetases. Daniel Y. Dubois, Jacques Lapointe and Shun-ichi Sekine. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 10: Glutamyl-tRNA Synthetases. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. de Pouplana, Lluıs Ribas, and Paul Schimmel. "Operational RNA code for amino acids in relation to genetic code in evolution." Journal of Biological Chemistry 276.10 (2001): 6881-6884. Raczniak, Gregory, et al. "A single amidotransferase forms asparaginyl-tRNA and glutaminyl-tRNA in Chlamydia trachomatis." Journal of Biological Chemistry 276.49 (2001): 45862-45867. Perona, John J., and Andrew Hadd. "Structural diversity and protein engineering of the aminoacyl-tRNA synthetases." Biochemistry 51.44 (2012): 8705-8729. Wolf, Yuri I., et al. "Evolution of aminoacyl-tRNA synthetases—analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events." Genome research 9.8 (1999): 689-710. Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Hadd, Andrew, and John J. Perona. "Coevolution of specificity determinants in eukaryotic glutamyl-and glutaminyl-tRNA synthetases." Journal of molecular biology 426.21 (2014): 3619-3633. Lapointe JA, Duplain LO, Proulx MA. A single glutamyl-tRNA synthetase aminoacylates tRNAGlu and tRNAGln in Bacillus subtilis and efficiently misacylates Escherichia coli tRNAGln1 in vitro. Journal of Bacteriology. 1986 Jan;165(1):88-93. Kim, Taeho, et al. "Catalytic peptide of human glutaminyl-tRNA synthetase is essential for its assembly to the aminoacyl-tRNA synthetase complex." Journal of Biological Chemistry 275.28 (2000): 21768-21772. Rath, Virginia L., et al. "How glutaminyl-tRNA synthetase selects glutamine." Structure 6.4 (1998): 439-449. Rould, M. A., J. J. Perona, and T. A. Steitz. "Structural basis of anticodon loop recognition by glutaminyl-tRNA synthetase." Nature 352.6332 (1991): 213-218. Nureki, Osamu, et al. "Structure of an archaeal non-discriminating glutamyl-tRNA synthetase: a missing link in the evolution of Gln-tRNAGln formation." Nucleic acids research 38.20 (2010): 7286-7297. Siatecka, Miroslawa, et al. "Modular evolution of the Glx‐tRNA synthetase family: Rooting of the evolutionary tree between the bacteria and archaea/eukarya branches." European Journal of Biochemistry 256.1 (1998): 80-87.