Molecular Mechanism Governing Ratio-dependent Transcription Regulation in the CcdAB Operon

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Mar 24

PMID 28334797

Citations 16

Authors

Alexandra Vandervelde

Igor Drobnak

San Hadzi

Yann G-J Sterckx

Thomas Welte

Henri De Greve

Daniel Charlier

Rouslan Efremov

Remy Loris

Jurij Lah

Affiliations

Soon will be listed here.

Abstract

Bacteria can become transiently tolerant to several classes of antibiotics. This phenomenon known as persistence is regulated by small genetic elements called toxin-antitoxin modules with intricate yet often poorly understood self-regulatory features. Here, we describe the structures of molecular complexes and interactions that drive the transcription regulation of the ccdAB toxin-antitoxin module. Low specificity and affinity of the antitoxin CcdA2 for individual binding sites on the operator are enhanced by the toxin CcdB2, which bridges the CcdA2 dimers. This results in a unique extended repressing complex that spirals around the operator and presents equally spaced DNA binding sites. The multivalency of binding sites induces a digital on-off switch for transcription, regulated by the toxin:antitoxin ratio. The ratio at which this switch occurs is modulated by non-specific interactions with the excess chromosomal DNA. Altogether, we present the molecular mechanisms underlying the ratio-dependent transcriptional regulation of the ccdAB operon.

Citing Articles

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Toxin:antitoxin ratio sensing autoregulation of the module.

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