General stress response in α‐proteobacteria: PhyR and beyond

SummaryIn addition to stress‐specific responses, most bacteria can mount a general stress response (GSR), which protects the cells against a wide range of unspecific stress conditions. The best‐understood examples of GSR are the σB‐cascade of Bacillus subtilis and the RpoS response in Escherichia coli. While the latter is conserved in many other proteobacteria of the β‐, γ‐ and δ‐clades, RpoS homologues are absent in α‐proteobacteria and their GSR has long been a mystery. Recent publications finally unraveled the core of the GSR in this proteobacterial class, which is mediated by EcfG‐like σ‐factors. EcfG activity is controlled by NepR‐like anti‐σ factors and PhyR‐like proteins that act as anti‐anti‐σ factors. These unusual hybrid proteins contain an N‐terminal EcfG‐like domain that acts as a docking interface for NepR, and a C‐terminal receiver domain typical for bacterial response regulators. Upon phosphorylation, PhyR titrates NepR away from EcfG, thereby releasing the σ‐factor to recruit RNA polymerase and initiate transcription of its target genes. In this issue of Molecular Microbiology, Herrou et al. describe the function and three‐dimensional structure of PhyR from Caulobac