Phenylalanyl-tRNA Synthetase β Subunit (Archaeal-like)

The archaeal-like phenylalanyl-tRNA synthetase (PheRS-A) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid phenylalanine to its cognate tRNA: $ \text{Phe} + \text{tRNA}^\text{Phe} + \text{ATP} \xrightarrow{\text{PheRS-A}} \text{Phe-tRNA}^\text{Phe} + \text{AMP} + \text{PP}_i $ The phenylalanyl-tRNA synthetases (PheRS) are considered to be one of the most evolutionarily complex enzymes among aminoacyl-tRNA synthetases (Klipcan et al. 2010). Unlike most Class II synthetases, which are homodimeric, PheRS-A operates as a heterotetramer composed of two $\alpha$ and two $\beta$ subunits $\alpha_2 \beta_2$. There are three known variants of PheRS: one found predominantly in eukaryotes/archaea, one found in bacteria [PheRS-B](/class2/phe1), and one localized to eukaryotic organelles [PheRS-M](/class2/phe5). This page specifically refers to the $\beta$ subunit of the archaral-like variant (PheRS-A$\beta$). The catalytic activity and tRNA recognition of PheRS-A is restricted to the $\alpha$ subunit, while editing activity is restricted to the β subunit, which is over twice the size of the α subunit (Fishman et al. 2001). The only other tetrameric member of Class II is the bacterial [GlyRS-B](/class2/gly2), which is also composed of two catalytic $\alpha$ subunits and two non-catalytic $\beta$ subunits. Although both subunits of PheRS-A possess a Class II catalytic domain, catalytic activity appears to be restricted to the $\alpha$ subunit. tRNA recognition also occurs in the $\alpha$ chain (in contrast to the bacterial tetramer for which tRNA binding occurs in the [β chain](/class2/phe2/), while editing activity is restricted to $\beta$. The editing domain (hB3 and hB4) is located near the N-terminal and resembles that of PheRS-Bβ (Finarov et al. 2010), which is known to target mischarged tyrosines (Roy et al. 2004). The catalytic domain does not appear to possess catalytic activity (Fishman et al. 2001), but still contains the six antiparallel strands characteristic of a Class II AARS. As such, the sequence at the structural positions of motifs 1, 2, and 3 do not follow the motif patterns. The positions one would normally expect to see these motifs are labeled below for convenience.

References

Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Klipcan, Liron, et al. "Structural aspects of phenylalanylation and quality control in three major forms of phenylalanyl-tRNA synthetase." Journal of amino acids 2010 (2010). Finarov, Igal, et al. "Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns." Structure 18.3 (2010): 343-353. Fishman, Roman, et al. "Structure at 2.6 Å resolution of phenylalanyl-tRNA synthetase complexed with phenylalanyl-adenylate in the presence of manganese." Acta Crystallographica Section D: Biological Crystallography 57.11 (2001): 1534-1544. Kavran, Jennifer M., et al. "Structure of pyrrolysyl-tRNA synthetase, an archaeal enzyme for genetic code innovation." Proceedings of the National Academy of Sciences 104.27 (2007): 11268-11273. Cusack, Stephen, Michael Härtlein, and Reuben Leberman. "Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases." Nucleic acids research 19.13 (1991): 3489-3498. Valencia-Sánchez, Marco Igor, et al. "Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases." Journal of Biological Chemistry 291.28 (2016): 14430-14446. Safro, Mark. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 22: Phenylalanyl-tRNA Synthetases. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. Perona, John J., and Andrew Hadd. "Structural diversity and protein engineering of the aminoacyl-tRNA synthetases." Biochemistry 51.44 (2012): 8705-8729. Roy, Herve, et al. "Post‐transfer editing in vitro and in vivo by the β subunit of phenylalanyl‐tRNA synthetase." The EMBO journal 23.23 (2004): 4639-4648.