A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT

Nature Communications
Ariel TalaveraRemy Loris

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 aT toxicity. GraTA represents a TA module where a flexible region in the toxin rather than in the antitoxin controls operon expression and toxin activity.

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Citations

Jan 15, 2020·Journal of Bacteriology·Nathan FraikinLaurence Van Melderen
Oct 19, 2019·Biomolecular NMR Assignments·Maruša Prolič-KalinšekAlexander N Volkov
Sep 10, 2019·Structure·Melek Cemre ManavDitlev Egeskov Brodersen
Apr 1, 2021·Protein Science : a Publication of the Protein Society·Pieter De BruynRemy Loris
Jul 2, 2021·Acta Crystallographica. Section D, Structural Biology·Gabriela Garcia-RodriguezRemy Loris
Jan 4, 2022·Nature Reviews. Microbiology·Dukas JurėnasLaurence Van Melderen

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Methods Mentioned

BETA
Isothermal titration calorimetry
size exclusion chromatography
X-ray
gel filtration
electrophoresis

Software Mentioned

XDSME
PHENIX
XDS
MolProbity
GraT
MicroCal Origin
ATSAS
GraA
GraTA
PHASER

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