Publication
Title
Molecular mechanism governing ratio-dependent transcription regulation in the ccdAB operon
Author
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.
Language
English
Source (journal)
Nucleic acids research. - London
Publication
London : 2017
ISSN
0305-1048
1362-4962
Volume/pages
45 :6 (2017) , p. 2937-2950
ISI
000398376200011
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Project info
ESRF and DUBBLE: Synchrotron X-rays for revealing the structure and function of molecules and materials.
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 04.10.2018
Last edited 26.09.2021