Rv0474 is a copper‐responsive transcriptional regulator that negatively regulates expression of RNA polymerase β subunit in Mycobacterium tuberculosis.

Autor: Raghunandanan, Sajith, Ramachandran, Ranjit, Gomez, Roshna Lawrence, Devanarayanan, Sivasankar, Bommakanti, Akhila, Kondapi, Anand Kumar, Varadarajan, Raghavan, Kumar, Ramakrishnan Ajay
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Zdroj: FEBS Journal; Oct2018, Vol. 285 Issue 20, p3849-3869, 21p
Abstrakt: 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. Under standard growth conditions Rv0474 is bound to its own promoter near the transcription start site, thus preventing RNA polymerase from binding, and the gene is transcriptionally repressed. In the presence of elevated amounts of copper, the copper‐bound Rv0474 undergoes a conformational change which prevents the protein from binding to its own promoter. Relieved of repression, Rv0474 undergoes transcription. Copper‐bound Rv0474 then binds to rpoB promoter and represses the expression of rpoB possibly leading to the repression of critical genes, and thus driving MTB to growth arrest and persistence. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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