Sigma E monitors and responds to changes in OMP folding. Under nonstressed conditions, E is inactivated through membrane sequestration via interactions with the membrane spanning -sigma factor, RseA. Envelope perturbations that disrupt the OMP folding pathway alleviate the negative interaction between sigmaE and RseA. This is accomplished by misfolded OMPs weakening the interaction between RseA and E, and misfolded OMPs further weaken this interaction by direct or indirect association with RseA, leading to full activation of the pathway. SigmaE is released from RseA, associates with RNA polymerase (RNAP) holoenzyme and activates transcription from the promoters of downstream targets, which include OMP folding and degrading factors FkpA (peptidyl-prolyl-isomerase) and DegP (periplasmic protease), rpoH (sigma32) , the rpoE (sigma24), rseAC (sigmaE or rpoE negative regulatory protein) operon, virulence genes, and others yet to be identified. Autoregulation amplifies the response and allows for rapid shut-off once the misfolded OMPs have been cleared through overproduction of the negative regulators RseA.
* This figure was modified from (25)