AbmR (Rv1265) is a novel transcription factor of Mycobacterium tuberculosis that regulates host cell association and expression of the non-coding small RNA Mcr11.
Mol Microbiol
; 110(5): 811-830, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30207611
ABSTRACT
Gene regulatory networks used by Mycobacterium tuberculosis (Mtb) during infection include many genes of unknown function, confounding efforts to determine their roles in Mtb biology. Rv1265 encodes a conserved hypothetical protein that is expressed during infection and in response to elevated levels of cyclic AMP. Here, we report that Rv1265 is a novel auto-inhibitory ATP-binding transcription factor that upregulates expression of the small non-coding RNA Mcr11, and propose that Rv1265 be named ATP-binding mcr11 regulator (AbmR). AbmR directly and specifically bound DNA, as determined by electrophoretic mobility shift assays, and this DNA-binding activity was enhanced by AbmR's interaction with ATP. Genetic knockout of abmR in Mtb increased abmR promoter activity and eliminated growth phase-dependent increases in mcr11 expression during hypoxia. Mutagenesis identified arginine residues in the carboxy terminus that are critical for AbmR's DNA-binding activity and gene regulatory function. Limited similarity to other DNA- or ATP-binding domains suggests that AbmR belongs to a novel class of DNA- and ATP-binding proteins. AbmR was also found to form large organized structures in solution and facilitate the serum-dependent association of Mtb with human lung epithelial cells. These results indicate a potentially complex role for AbmR in Mtb biology.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Fatores de Transcrição
/
Proteínas de Transporte
/
Pequeno RNA não Traduzido
/
Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Mol Microbiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
MICROBIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos