Discrete Structural Dynamics of Pseudo-Palindromic Motifs Control DNA Binding of Bacterial Toxin-Antitoxin Complexes

Toxin-antitoxin (TA) systems have been strongly implicated in bacterial cell survival during antibiotic stress and are likely to play important roles in persister cell formation1,2. Understanding the function and regulation of TA systems will thus be vital for combatting chronic and recurrent human infections in the future. Expression of type II TA systems is regulated at the transcriptional level through direct binding of the antitoxin to pseudo-palindromic sequences on operator DNA. In this process, the toxin functions as a co-repressor by stimulating DNA binding through direct interaction with the antitoxin and formation of a higher-order protein complex3. In the VapBC TA class, the VapC toxin is inhibited by direct protein interaction with the VapB antitoxin, which also contains a DNA binding domain of the AbrB type3. Since TA complexes show a great structural variety and no structures have been determined of the same system both on and off DNA, the structural changes occurring upon DNA binding are no...