CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator | Academic Article individual record
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 (S(2)N) Cu(I) complex. The 2.6-A 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.

author list (cited authors)
Liu, T., Ramesh, A., Ma, Z., Ward, S. K., Zhang, L., George, G. N., ... Giedroc, D. P.
publication date
2007
published in
keywords
  • Operon
  • Bacterial Proteins
  • Mycobacterium Tuberculosis
  • Spectrum Analysis
  • Molecular Sequence Data
  • Transcription, Genetic
  • Transcription Factors
  • Gene Expression Regulation, Bacterial
  • Copper
  • Sequence Homology, Amino Acid
  • Crystallography, X-Ray
  • X-rays
  • Amino Acid Sequence
altmetric score

4.5

citation count

233