Structural insights into the <i>Shigella flexneri</i><scp>G</scp>mv<scp>AT</scp> toxin‐antitoxin system

Toxin-antitoxin (TA) systems are common bicistronic gene elements in bacteria and are critical for stress responses. The toxin members of the GNAT/RHH TA family can acetylate certain aminoacylated tRNA molecules and inhibit global protein translation. One member named GmvT is important for virulence plasmid maintenance in Shigella flexneri, but the underlying mechanism remains poorly understood. Here, we report the cocrystal structures of GmvT in two forms. The binding of the antitoxin mainly relies on the backbone of the toxin while the cofactor is free of contacts with the antitoxin, supported by follow-up in vitro and in vivo studies. Our study provides insight into the protein-protein/protein-ligand interactions of the GmvAT pair and the structural basis for molecular recognition.