Abstract
Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. A typical regulatory strategy involves the antitoxin binding and repressing its own promoter while the toxin often acts as a co-repressor. Here we show that Pseudomonas putida graTA-encoded antitoxin GraA and toxin GraT differ from other TA proteins in the sense that not the antitoxin but the toxin possesses a flexible region. GraA auto-represses the graTA promoter: two GraA dimers bind cooperatively at opposite sides of the operator sequence. Contrary to other TA modules, GraT is a de-repressor of the graTA promoter as its N-terminal disordered segment prevents the binding of the GraT2A2 complex to the operator. Removal of this region restores operator binding and abrogates Gr\taT toxicity. GraTA represents a TA module where a flexible region in the toxin rather than in the antitoxin controls operon expression and toxin activity.
Highlights
Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress
For many type II TA systems repression depends on the ratio between toxin and antitoxin by a mechanism known as conditional cooperativity[8,9,10]
GraTA (Growth rate affecting Toxin–Antitoxin) is a type II TA module recently discovered in Pseudomonas putida[18]
Summary
Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. Contrary to other TA modules, GraT is a de-repressor of the graTA promoter as its N-terminal disordered segment prevents the binding of the GraT2A2 complex to the operator. The production of type II TA proteins is auto-regulated at the level of transcription Their antitoxins are typically composed of two domains: a DNA binding domain next to an (often intrinsically disordered) toxin neutralizing domain[7]. We show that GraA does not contain unstructured regions and forms a globular dimer while the toxin GraT contains an N-terminal intrinsically disordered region that is key for transcriptional regulation of the graTA operon as well as for the RNase activity of GraT. GraA binds tightly to the graTA operator and GraT prevents this interaction through steric interference from its N-terminal disordered region. GraTA represents a type of TA module where intrinsically disordered region in the toxin rather than in the antitoxin controls both operon expression and toxin activity
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