Arginyl-tRNA Synthetase

Arginyl-tRNA synthetase (ArgRS) is a homodimeric enzyme that plays a crucial role in protein synthesis by catalysing the attachment of the amino acid arginine to its cognate tRNA: $ \text{Arg} + \text{tRNA}^\text{Arg} + \text{ATP} \xrightarrow{\text{ArgRS}} \text{Arg-tRNA}^\text{Arg} + \text{AMP} + \text{PP}_i $ In contrast to most Class I and II aminoacyl-tRNA synthetases, ArgRS requires the presence of $\text{tRNA}^\text{Arg}$ for effective arginine activation (Mitra et al. 1967, Eriani and Cavarelli 2005). tRNA binding is coordinated by the N- and C-terminal domains, which are adjacent in the tertiary structure (Cavarelli et al. 1998). The N-terminal domain is a two layer α/β unit that recognises the D-loop, and the C-terminal domain is a four helix bundle that recognises the anticodon. Structural and mutation studies suggest that the interaction between the N-terminal domain and the D-loop are not stable, and deletion of the N-terminal domain has only a small effect on tRNA aminoacylation activity (Konno et al. 2009). Furthermore, the orientation of this domain relative to the catalytic domain also varies across structures (Shimada et al.2001). The N-terminal domain is characteristic of ArgRS and is lacking in other Class I structures, while the C-terminal [anticodon binding domain](/superfamily/class1/Anticodon_binding_domain_CRIMVL) is also found in [CysRS](/class1/cys), [LeuRS](/class1/leu1), [ValRS](/class1/val), [MetRS](/class1/met), and [IleRS](/class1/ile). ArgRS charges tRNAs that correspond to six different codons. In the standard genetic code, leucine and serine are the only other amino acids which are encoded by six codons. The catalytic domain of ArgRS is typical of a Class I aminoacyl-tRNA synthetase, with a four-stranded Rossmann fold. Arginine binding in the active site is coordinated by two salt bridges (with two acidic residues) and one hydrogen bond (with a tyrosine) and these three residues are strongly conserved in ArgRS (Cavarelli et al. 1998). Like most members of the superfamily, ATP binding is coordinated by the backbone brackets (Kaiser et al. 2018). ArgRS is characterised by a bundle of $\alpha$ helices after the HIGH motif - the ArgRS insertion module (Cavarelli et al. 1998, Douglas et al. 2023). The number of helices in the bundle is variable. The catalytic domain is not immediately related to any other aminoacyl-tRNA synthetases, and as such, ArgRS falls into its own subclass, Ie (Douglas et al. 2023). While most Class I aminoacyl-tRNA synthetases are monomeric, ArgRS is homodimeric. In some archaea, this dimer assembles into a complex with [SerRS](/class2/ser1), which has been reported to increase the efficiency of SerRS under extreme conditions (Godinic-Mikulcic et al. 2011). It appears that ArgRS lacks editing activity (Gomez and Ibba 2020).

References

Kaiser, Florian, et al. "Backbone brackets and arginine tweezers delineate class I and class II aminoacyl tRNA synthetases." PLoS computational biology 14.4 (2018): e1006101. Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Cavarelli, Jean, et al. "L-arginine recognition by yeast arginyl-tRNA synthetase." The EMBO journal 17.18 (1998): 5438-5448. Konno, Michiko, et al. "Modeling of tRNA‐assisted mechanism of Arg activation based on a structure of Arg‐tRNA synthetase, tRNA, and an ATP analog (ANP)." The FEBS journal 276.17 (2009): 4763-4779. Shimada, Atsushi, et al. "Structural and mutational studies of the recognition of the arginine tRNA-specific major identity element, A20, by arginyl-tRNA synthetase." Proceedings of the National Academy of Sciences 98.24 (2001): 13537-13542. Eriani, Gilbert, and Jean Cavarelli. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 2: Arginyl-tRNA Synthetases. Mitra, Samir K., and Alan H. Mehler. "The arginyl transfer ribonucleic acid synthetase of Escherichia coli." Journal of Biological Chemistry 242.23 (1967): 5490-5494. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. Godinic-Mikulcic, Vlatka, et al. "An archaeal tRNA-synthetase complex that enhances aminoacylation under extreme conditions." Journal of Biological Chemistry 286.5 (2011): 3396-3404.