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- Title
CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator.
- Authors
Tong Liu; Ramesh, Arati; Zhen Ma; Ward, Sarah K.; Limei Zhang; George, Graham N.; Talaat, Adel M.; Sacchettini, James C.; Giedroc, David P.
- Abstract
Copper is an essential element that becomes highly cytotoxic when concentrations exceed the capacity of cells to sequester the ion. Here, we identify a new copper-specific repressor (CsoR) of a copper-sensitive operon (cso) in Mycobacterium tuberculosis (Mtb) that is representative of a large, previously uncharacterized family of proteins (DUF156). Electronic and X-ray absorption spectroscopies reveal that CsoR binds a single-monomer mole equivalent of Cu(I) to form a trigonally coordinated (S2N) Cu(I) complex. The 2.6-Å crystal structure of copper-loaded CsoR shows a homodimeric antiparallel four-helix bundle architecture that represents a novel DNA-binding fold. The Cu(I) is coordinated by Cys36, Cys65′ and His61′ in a subunit bridging site. Cu(I) binding negatively regulates the binding of CsoR to a DNA fragment encompassing the operator-promoter region of the Mtb cso operon; this results in derepression of the operon in Mtb and the heterologous host Mycobacterium smegmatis. Substitution of Cys36 or His61 with alanine abolishes Cu(I)- and CsoR-dependent regulation in vivo and in vitro. Potential roles of CsoR in Mtb pathogenesis are discussed.
- Publication
Nature Chemical Biology, 2007, Vol 3, Issue 1, p60
- ISSN
1552-4450
- Publication type
Academic Journal
- DOI
10.1038/nchembio844