The crystal structure of the anti-σ factor CnrY in complex with the σ factor CnrH shows a new structural class of anti-σ factors targeting extracytoplasmic function σ factors

J Mol Biol. 2014 Jun 12;426(12):2313-27. doi: 10.1016/j.jmb.2014.04.003. Epub 2014 Apr 12.


Gene expression in bacteria is regulated at the level of transcription initiation, a process driven by σ factors. The regulation of σ factor activity proceeds from the regulation of their cytoplasmic availability, which relies on specific inhibitory proteins called anti-σ factors. With anti-σ factors regulating their availability according to diverse cues, extracytoplasmic function σ factors (σ(ECF)) form a major signal transduction system in bacteria. Here, structure:function relationships have been characterized in an emerging class of minimal-size transmembrane anti-σ factors, using CnrY from Cupriavidus metallidurans CH34 as a model. This study reports the 1.75-Å-resolution structure of CnrY cytosolic domain in complex with CnrH, its cognate σ(ECF), and identifies a small hydrophobic knob in CnrY as the major determinant of this interaction in vivo. Unsuspected structural similarity with the molecular switch regulating the general stress response in α-proteobacteria unravels a new class of anti-σ factors targeting σ(ECF). Members of this class carry out their function via a 30-residue stretch that displays helical propensity but no canonical structure on its own.

Keywords: bacterial transcription; metal resistance; protein:protein interaction; sigma factor; transmembrane signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Cupriavidus / chemistry
  • Cupriavidus / enzymology*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Repressor Proteins / chemistry*
  • Repressor Proteins / metabolism*
  • Sigma Factor / antagonists & inhibitors*
  • Sigma Factor / chemistry*


  • Repressor Proteins
  • Sigma Factor

Associated data

  • PDB/4CXF