The C-terminal domain of the archaeal leucyl-tRNA synthetase prevents misediting of isoleucyl-tRNAIle

Ryuya Fukunaga, Shigeyuki Yokoyama

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


In the archaeal leucyl-tRNA synthetase (LeuRS), the C-terminal domain recognizes the long variable arm of tRNALeu for aminoacylation, and the so-called editing domain deacylates incorrectly formed Ile-tRNA Leu. We previously reported, for Pyrococcus horikoshii LeuRS, that a deletion mutant lacking the C-terminal domain (LeuRS_Δ(811-967)) retains normal editing activity, but has severely reduced aminoacylation activity. In this study, we found that LeuRS_Δ(811-967), but not the wild-type LeuRS, exhibited surprisingly robust deacylation activity against Ile-tRNA Ile, correctly formed by isoleucyl-tRNA synthetase ("misediting"). Structural superposition of tRNAIle onto the LeuRS·tRNALeu complex indicated that Ile911, Lys912, and Glu913 of the LeuRS C-terminal domain clash with U20 of tRNAIle, which is bulged out as compared to the corresponding nucleotide of tRNA Leu. The deletion of amino acid residues 911-913 of LeuRS enhanced the Ile-tRNAIle deacylation activity, without affecting the Ile-tRNALeu deacylation activity. These results demonstrate that the clashing between U20 of tRNAIle, and residues 911-913 of the LeuRS C-terminal domain is the structural mechanism that prevents misediting. In contrast, the deletion of the C-terminal domains of the isoleucyl- and valyl-tRNA synthetases impaired both the aminoacylation (Ile-tRNAIle and Val-tRNA Val formation, respectively) and editing (Val-tRNAIle and Thr-tRNAVal deacylation, respectively) activities, and did not cause misediting (Val-tRNAVal and Thr-tRNAThr deacylation, respectively) activity. Thus, the requirement of the C-terminal domain for misediting prevention is unique to LeuRS, which does not recognize the anticodon of the cognate tRNA, unlike the common aminoacyl-tRNA synthetases.

Original languageEnglish (US)
Pages (from-to)4985-4996
Number of pages12
Issue number17
StatePublished - May 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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