Molecular basis of glycyl-tRNAGly acetylation by TacT from Salmonella Typhimurium

Abstract

Bacterial toxin-antitoxin modules contribute to the stress adaptation, persistence, and dormancy of bacteria for survival under environmental stresses and are involved in bacterial pathogenesis. In Salmonella Typhimurium, the Gcn5-related N-acetyltransferase toxin TacT reportedly acetylates the α-amino groups of the aminoacyl moieties of several aminoacyl-tRNAs, inhibits protein synthesis, and promotes persister formation during the infection of macrophages. Here, we show that TacT exclusively acetylates Gly-tRNA^Glyin vivo and in vitro. The crystal structure of the TacT:acetyl-Gly-tRNA^Gly complex and the biochemical analysis reveal that TacT specifically recognizes the discriminator U73 and G71 in tRNA^Gly, a combination that is only found in tRNA^Gly isoacceptors, and discriminates tRNA^Gly from other tRNA species. Thus, TacT is a Gly-tRNA^Gly-specific acetyltransferase toxin. The molecular basis of the specific aminoacyl-tRNA acetylation by TacT provides advanced information for the design of drugs targeting Salmonella.

Keywords: Gcn5-related acetyltransferase; Salmonella; TacT; aminoacyl-tRNA; mechanism; pathogen; persister formation; specificity; structure; toxin-antitoxin.