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

Gene expression in bacteria is regulated at the level of transcription initiation, a process driven by a factors. The regulation of a factor activity proceeds from the regulation of their cytoplasmic availability, which relies on specific inhibitory proteins called anti-sigma factors. With anti-sigma factors regulating their availability according to diverse cues, extracytoplasmic function sigma factors (sigma(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-a factors, using CnrY from Cupriavidus metallidurans CH34 as a model. This study reports the 1.75-angstrom-resolution structure of CnrY cytosolic domain in complex with CnrH, its cognate sigma(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 alpha-proteobacteria unravels a new class of anti-sigma factors targeting sigma(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. (C) 2014 Elsevier Ltd. All rights reserved.