Aminoacyl‐tRNA Synthetases

John G Arnez, University of Louisville, Louisville, Kentucky, USA
Dino Moras, Universit de Strasbourg, Strasbourg, France

Published online: September 2009

DOI: 10.1002/9780470015902.a0000530.pub2

Aminoacyl-tRNA synthetases catalyse a key reaction in protein biosynthesis. They match the 20 amino acids to the genetic code by specifically attaching them to their adaptors, transfer ribonucleic acid (tRNA) molecules. The reaction proceeds in two steps: the amino acid is first activated by adenosine triphosphate (ATP) to form aminoacyl adenylate, and then the aminoacyl group is transferred to the terminal ribose of tRNA. This family of enzymes is divided into two classes, based on the similarities in primary structure and architecture of the active site domains; the two architectures are characterized by two modes of binding of ATP, the intermediate aminoacyl adenylate and the acceptor end of tRNA, which result in two regioselectivities of amino acid attachment to the terminal ribose of the tRNA. Aminoacyl-tRNA synthetases are modular enzymes; to the central active site module are attached various domains with diverse functions such as tRNA-binding and amino acid editing. The primary subject of this article are structural and functional aspects of these enzymes.

Key Concepts

  • Aminoacylation is a key reaction in protein biosynthesis, as it matches the standard 20 amino acids to the genetic code.
  • Aminoacylation is generally catalysed by aminoacyl-tRNA synthetases, a family of 20 enzymes, one for each standard amino acid and a set of corresponding (cognate isoacceptor) tRNAs.
  • Aminoacylation proceeds in two steps, where the amino acid is first activated by ATP to form aminoacyl adenylate, a mixed anhydride, and then transferred to form an ester bond with the terminal ribose of tRNA.
  • Aminoacyl-tRNA synthetases are divided into two classes, based on the similarities in primary structure (sequence) and architecture of their active site domains.
  • Aminoacyl-tRNA synthetases are modular enzymes; to the central active site module are attached various domains with diverse functions such as tRNA-binding and amino acid editing.
  • Aminoacyl-tRNA synthetases are highly specific enzymes, attaching the correct amino acids to the corresponding tRNAs with high fidelity.
  • Aminoacyl-tRNA synthetases of the two classes generally bind the acceptor arm of tRNA in two ways that constitute mirror images of each other, resulting in two different regioselectivities of amino acid attachment to the tRNA.

Keywords: structure and function; aminoacylation; translation; protein synthesis; transfer ribonucleic acid (tRNA)

Figure 1. Active site domains of aminoacyl-tRNA synthetases complexed with the acceptor arms of their cognate tRNAs. Shown also are ATP and key interactions with tRNA. (a) Class I glutaminyl-tRNA synthetase. The nucleotide-binding fold (the Rossmann fold) is shown in yellow. The two class I characteristic motifs HIGH and KMSKS are highlighted in red and blue, respectively. (b) Class II aspartyl-tRNA synthetase. The three class II characteristic motifs are highlighted: motif 1 in red, motif 2 in green and motif 3 in blue. The insertion modules, shown in light blue, provide additional binding elements for the tRNA; in some enzymes they contain editing activities. Adapted from Arnez JG and Moras D (1997) Structural and functional considerations of the aminoacylation reaction. Trends in Biochemical Sciences 22: 211–216. Copyright © 1997 with permission from Elsevier Science.
Figure 2. Modular organization of aminoacyl-tRNA synthetases and mirror-symmetrical binding modes characteristic of the two classes. The tRNAs of glutaminyl-tRNA synthetase:tRNAGln complex (class I, left) and aspartyl-tRNA synthetase:tRNAAsp complex (class II, right) were superposed on tRNAPhe (the first tRNA known in three-dimensional structural detail and commonly used as reference, middle). The two enzymes were then translated away from tRNAPhe for this picture; the variable loop and CCA end are highlighted in blue and green, respectively. The enzyme modules are rendered as follows: the core active site domains in yellow, the active site insertions in light blue, the linkers in green and the anticodon-binding domains in orange. Adapted from Arnez JG and Moras D (1997) Structural and functional considerations of the aminoacylation reaction. Trends in Biochemical Sciences 22: 211–216. Copyright © 1997 with permission from Elsevier Science.
Figure 3. Areas of tRNAs that interact with cognate aminoacyl-tRNA synthetases. In each case, nucleotides whose bases form direct hydrogen bonds with the enzyme are shown in red, nucleotides that enable the tRNA to attain the conformation needed for productive interaction with the enzyme are drawn in green and the portions of the phosphodiester backbone in contact with the enzyme are highlighted as purple spheres. (a) tRNAGln, (b) tRNAAsp and (c) tRNASer.
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 Further Reading
    Arnez JG and Cavarelli J (1997) Structures of RNA-binding proteins. Quarterly Review of Biophysics 30: 195–240.
    Carter CW Jr (1993) Cognition, mechanism, and evolutionary relationships in aminoacyl-tRNA synthetases. Annual Review of Biochemistry 62: 715–748.
    Francklyn CS (2008) DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression. Biochemistry 47: 11695–11703.
    book Ibba M, Francklyn CS and Cusack S (eds) (2005) The Aminoacyl-tRNA Synthetases. Georgetown, TX: Landes Bioscience.
    Ibba M and Soll D (2000) Aminoacyl-tRNA synthesis. Annual Review of Biochemistry 69: 617–650.
    book Meinnel T, Mechulam Y and Blanquet S (1995) "Aminoacyl-tRNA synthetase: occurrence, structure, and function" In: Söll D and RajBhandary UL (eds) tRNA: Structure, Biosynthesis and Function, pp. 251–291. Washington, DC: American Society for Microbiology.
    Moras D (1992) Structural and functional relationships between aminoacyl-tRNA synthetases. Trends in Biochemical Sciences 17: 159–164.
    Perona JJ and Hou Y-M (2007) Indirect readout of tRNA for aminoacylation. Biochemistry 46: 10419–10432.
    Schimmel P and Söll D (1979) Aminoacyl-tRNA synthetases: general features and recognition of transfer RNAs. Annual Review of Biochemistry 48: 601–648.

Related Sub-Topics:

Protein Structure | Biomolecular Interactions | Enzymes: Structure and Action Mechanism
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Article Title: Aminoacyl‐tRNA Synthetases
 
How to Cite close
Arnez, John G, and Moras, Dino(Sep 2009) Aminoacyl‐tRNA Synthetases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000530.pub2]