Interdomain communication modulates the tRNA-dependent pre-transfer editing of leucyl-tRNA synthetase

Biochem J. 2013 Jan 1;449(1):123-31. doi: 10.1042/BJ20121258.


EcLeuRS [Escherichia coli LeuRS (leucyl-tRNA synthetase)] has evolved both tRNA-dependent pre- and post-transfer editing capabilities to ensure catalytic specificity. Both editing functions rely on the entry of the tRNA CCA tail into the editing domain of the LeuRS enzyme, which, according to X-ray crystal structural studies, leads to a dynamic disordered orientation of the interface between the synthetic and editing domains. The results of the present study show that this tRNA-triggered conformational rearrangement leads to interdomain communication between the editing and synthetic domains through their interface, and this communication mechanism modulates the activity of tRNA-dependent pre-transfer editing. Furthermore, tRNA-dependent editing reaction inhibits misactivating non-cognate amino acids from the synthetic active site. These results also suggested a novel quality control mechanism of EcLeuRS which is achieved through the co-ordination between the synthetic and editing domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Crystallography, X-Ray
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Leucine-tRNA Ligase / chemistry
  • Leucine-tRNA Ligase / genetics*
  • Leucine-tRNA Ligase / metabolism
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Tertiary / genetics
  • RNA Editing / genetics*
  • RNA, Transfer, Leu / chemistry
  • RNA, Transfer, Leu / genetics*
  • RNA, Transfer, Leu / metabolism


  • Escherichia coli Proteins
  • RNA, Transfer, Leu
  • Leucine-tRNA Ligase