Molecular mechanism governing ratio-dependent transcription regulation in the ccdAB operon.
Nucleic Acids Res
; 45(6): 2937-2950, 2017 04 07.
Article
em En
| MEDLINE
| ID: mdl-28334797
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 toxinantitoxin 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Óperon
/
Proteínas Repressoras
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Proteínas de Bactérias
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Toxinas Bacterianas
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Transcrição Gênica
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Regulação Bacteriana da Expressão Gênica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Bélgica