Alanyl tRNA Synthetase Domain Containing Protein 1 (AARSD1)

Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs;) has profound functional consequences. Throughout evolution, 2 editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, serine poses a bigger challenge than glycine. One checkpoint is the AlaRS editing center. The other is from widely distributed AlaXps (Aarsd1), free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid.