Molecular and Functional Dissection of a Putative RNA-binding Region in Yeast MitochondrialLeucyl-tRNA Synthetase

Mir Hussain Nawaz, Yan Ling Joy Pang, Susan A. Martinis

Research output: Contribution to journalArticlepeer-review


Aminoacylation and editing by leucyl-tRNA synthetases (LeuRS) require migration of the tRNA acceptor stem end between the canonical aminoacylation core and a separate domain called CP1 that is responsible for amino acid editing. The LeuRS CP1 domain can also support group I intron RNA splicing in the yeast mitochondria, although splicing-sensitive sites have been identified on the main body. The RDW peptide, a highly conserved peptide within an RDW-containing motif, resides near one of the β-strand linkers that connects the main body to the CP1 domain. We hypothesized that the RDW peptide was important for interactions of one or more of the LeuRS-RNA complexes. An assortment of X-ray crystallography structures suggests that the RDW peptide is dynamic and forms unique sets of interactions with the aminoacylation and editing complexes. Mutational analysis identified specific sites within the RDW peptide that failed to support protein synthesis activity in complementation experiments. In vitro enzymatic investigations of mutations at Trp445, Arg449, and Arg451 in yeast mitochondrial LeuRS suggested that these sites within the RDW peptide are critical to the aminoacylation complex, but impacted amino acid editing activity to a much less extent. We propose that these highly conserved sites primarily influence productive tRNA interactions in the aminoacylation complex.

Original languageEnglish (US)
Pages (from-to)384-394
Number of pages11
JournalJournal of Molecular Biology
Issue number2
StatePublished - Mar 23 2007


  • RNA splicing
  • amino acid editing
  • aminoacylation
  • group I intron
  • protein synthesis

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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