Disordered Toxin: The Mechanism Of Transcription Regulation Of The Pseudomonas Putida Grata Operon

Homeostasis of bacterial toxin-antitoxin (TA) systems is tightly regulated to maintain optimal growth in favorable conditions or growth arrest under stress. For type II TA systems one of the regulation steps comes from the ability of the antitoxin to bind its own TA operator and inhibit transcription. Here we propose a model for the transcription regulation for the TA module GraTA from Pseudomas putida. We show how one monomer from two independent GraA2 specifically bind into the major groove of the central palindrome of the graTA operator. Furthermore we demonstrate in the GraT2A2 complex the N‑terminal segment of GraT is disordered. This flexibility is responsible of braking down the GraA‑operator complex in-vitro and in-vivo, showing that the usage of structurally disordered regions is not exclusive for the antitoxins. In addition, toxins can also profit from the advantages of the disorder to play a role in the TA operon regulation.