Alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout its biology. Nevertheless, its C-terminal domain (C-Ala) is highly diverged and has been shown to play a role in either tRNA or DNA binding. Interestingly, we discovered that Caenorhabditis elegans cytoplasmic C-Ala (Ce-C-Ala(c)) robustly binds both ligands. How Ce-C-Ala(c) targets its cognate tRNA and whether a similar feature is conserved in its mitochondrial counterpart remain elusive. We show that the N- and C-terminal subdomains of Ce-C-Ala(c) are responsible for DNA and tRNA binding, respectively. Ce-C-Ala(c) specifically recognized the conserved invariant base G(18) in the D-loop of tRNA(Ala) through a highly conserved lysine residue, K934. Despite bearing little resemblance to other C-Ala domains, C. elegans mitochondrial C-Ala (Ce-C-Ala(m)) robustly bound both tRNA(Ala) and DNA and maintained targeting specificity for the D-loop of its cognate tRNA. This study uncovers the underlying mechanism of how C. elegans C-Ala specifically targets the D-loop of tRNA(Ala).
Date:
2023-08-09
Relation:
Journal of Biological Chemistry. 2023 Aug 9;299-302(9):Article number 105149.
