1. Rv0474 is a copper‐responsive transcriptional regulator that negatively regulates expression of <scp>RNA</scp> polymerase β subunit in Mycobacterium tuberculosis
- Author
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Ranjit Ramachandran, Ramakrishnan Ajay Kumar, Roshna Lawrence Gomez, Anand K. Kondapi, Sajith Raghunandanan, Sivasankar Devanarayanan, Raghavan Varadarajan, and Akhila Bommakanti
- Subjects
0301 basic medicine ,Leucine zipper ,Transcription, Genetic ,THP-1 Cells ,Sequence Homology ,Biochemistry ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,RNA polymerase ,Transcriptional regulation ,Humans ,Amino Acid Sequence ,Promoter Regions, Genetic ,Molecular Biology ,Psychological repression ,biology ,Chemistry ,Promoter ,DNA-Directed RNA Polymerases ,Gene Expression Regulation, Bacterial ,Cell Biology ,biology.organism_classification ,rpoB ,Molecular biology ,030104 developmental biology ,Copper ,Bacteria ,Transcription Factors - Abstract
We characterize Rv0474, a putative transcriptional regulatory protein of Mycobacterium tuberculosis, which is found to function as a copper-responsive transcriptional regulator at toxic levels of copper. It is an autorepressor, but at elevated levels (10-250 μm) of copper ions the repression is relieved resulting in an increase in Rv0474 expression. Copper-bound Rv0474 is recruited to the rpoB promoter leading to its repression resulting in the growth arrest of the bacterium. Mutational analysis showed that the helix-turn-helix and leucine zipper domains of Rv0474 are essential for its binding to Rv0474 and rpoB promoters, respectively. The mechanism of Rv0474-mediated rpoB regulation seems to be operational only in pathogenic mycobacteria that can persist inside the host.
- Published
- 2018