In depth analysis of the mechanism of action of metal-dependent sigma factors: characterization of CorE2 from Myxococcus xanthus

Nucleic Acids Res. 2016 Jul 8;44(12):5571-84. doi: 10.1093/nar/gkw150. Epub 2016 Mar 6.


Extracytoplasmic function sigma factors represent the third pillar of signal-transduction mechanisms in bacteria. The variety of stimuli they recognize and mechanisms of action they use have allowed their classification into more than 50 groups. We have characterized CorE2 from Myxococcus xanthus, which belongs to group ECF44 and upregulates the expression of two genes when it is activated by cadmium and zinc. Sigma factors of this group contain a Cys-rich domain (CRD) at the C terminus which is essential for detecting metals. Point mutations at the six Cys residues of the CRD have revealed the contribution of each residue to CorE2 activity. Some of them are essential, while others are either dispensable or their mutations only slightly affect the activity of the protein. However, importantly, mutation of Cys174 completely shifts the specificity of CorE2 from cadmium to copper, indicating that the Cys arrangement of the CRD determines the metal specificity. Moreover, the conserved CxC motif located between the σ2 domain and the σ4.2 region has also been found to be essential for activity. The results presented here contribute to our understanding of the mechanism of action of metal-dependent sigma factors and help to define new common features of the members of this group of regulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics*
  • Cadmium / metabolism
  • Copper / metabolism
  • Cysteine / genetics
  • Gene Expression Regulation, Bacterial / genetics
  • Mutation
  • Myxococcus xanthus / genetics*
  • Myxococcus xanthus / metabolism
  • Promoter Regions, Genetic
  • Sigma Factor / genetics*
  • Sigma Factor / metabolism
  • Trans-Activators / genetics*
  • Transcription, Genetic*
  • Zinc / metabolism


  • Bacterial Proteins
  • Sigma Factor
  • Trans-Activators
  • Cadmium
  • Copper
  • Zinc
  • Cysteine