Fig. 2

Native regulatory CpxAR two-component system countering IM stress in Escherichia coli (E. coli). Triggered by misfolded IMPs and IM damage, structural changes in the CpxA sensor domain cause the histidine kinase domain located in the cytoplasm to autophosphorylate. CpxA subsequently phosphorylates CpxR, the response regulator, activating it for transcriptional regulation. One of the activated genes encodes CpxP, which inhibits CpxA activation and functions in a negative-feedback loop. In parallel, the cpxP mRNA is further processed by RNase E to form the small RNA cpxQ that in turn post-transcriptionally reduces the synthesis of IMPs in the cytoplasm. IM inner membrane, OM outer membrane, IMP inner membrane proteins