An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis

In addition to their essential catalytic role in protein biosynthesis, amin oacyl-tRNA synthetases participate in numerous other functions, including r egulation of gene expression and amino acid biosynthesis via transamidation pathways. Herein, we describe a class of aminoacyl-tRNA synthetase-like (H isZ) proteins based on the catalytic core of the contemporary class II hist idyl-tRNA synthetase whose members lack aminoacylation activity but are ins tead essential components of the first enzyme in histidine biosynthesis ATP phosphoribosyltransferase (HisG), Prediction of the function of HisZ in La ctococcus lactis was assisted by comparative genomics, a technique that rev ealed a link between the presence or the absence of HisZ and a systematic v ariation in the length of the HisG polypeptide. HisZ is required for histid ine prototrophy, and three other lines of evidence support the direct invol vement of HisZ in the transferase function. (i) Genetic experiments demonst rate that complementation of an in-frame deletion of HisG from Escherichia coli (which does not possess HisZ) requires both HisG and HisZ from L. lact is, (ii) Coelution of HisG and HisZ during affinity chromatography provides evidence of direct physical interaction. (iii) Both HisG and HisZ are requ ired for catalysis of the ATP phosphoribosyltransferase reaction. This obse rvation of a common protein domain linking amino acid biosynthesis and prot ein synthesis implies an early connection between the biosynthesis bf amino acids and proteins.