Plasticity of recognition of the 3'-end of mischarged tRNA by class I aminoacyl-tRNA synthetases.
Certain aminoacyl-tRNA synthetases prevent potential errors in protein synthesis through deacylation of mischarged tRNAs. For example, the close homologs isoleucyl-tRNA synthetase (IleRS) and valyl-tRNA synthetase (ValRS) deacylate Val-tRNA(Ile) and Thr-tRNA(Val), respectively. Here we examined the chemical requirements at the 3'-end of the tRNA for these hydrolysis reactions. Single atom substitutions at the 2'- and 3'-hydroxyls of a variety of mischarged RNAs revealed that, while acylation is at the 2'-OH for both enzymes, IleRS catalyzes deacylation specifically from the 3'-OH and not from the 2'-OH. In contrast, ValRS can deacylate non-cognate amino acids from the 2'-OH. Moreover, for IleRS the specificity for a 3'-O location of the scissile ester bond could be forced to the 2'-position by introduction of a 3'-O-methyl moiety. Cumulatively, these and other results suggest that the editing sites of these class I aminoacyl-tRNA synthetases have a degree of inherent plasticity for substrate recognition. The ability to adapt to subtle differences in mischarged RNAs may be important for the high accuracy of aminoacylation.
Nordin
Brian E
BE
Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Schimmel
Paul
P
D000215:Acylation; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D017393:RNA Editing; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases