Periplasmic stress and ECF sigma factors

Envelope stress responses play important pysiological roles in a variety of processes, including protein folding, cell wall biosynthesis, and pathogen esis. Many of these responses are controlled by extracytoplasmic function ( ECF) sigma factors that respond to external signals by means of a membrane- localized anti-sigma factor. One of the best-characterized, ECF-regulated r esponses is the sigma (E) envelope stress response of Escherichia coli. The sigma (E) pathway ensures proper assembly of outer-membrane proteins (OMP) by controlling expression of genes involved in OMP folding and degradation in response to envelope stresses that disrupt these processes. Prevailing evidence suggests that, in E. coli, a second envelope stress response contr olled by the Cpx two-component system ensures proper pilus assembly. The se nsor kinase CpxA recognizes misfolded periplasmic proteins, such as those g enerated during pilus assembly, and transduces this signal to the response regulator CpxR through conserved phosphotransfer reactions. Phosphorylated CpxR activates transcription of periplasmic factors necessary for pilus ass embly.