A) Activation of CpxR by the cytoplasmic membrane sensor kinase CpxA. OM, outer membrane; IM, inner membrane. Upon activation by diverse extracytoplasmic signals (thunderbolt), CpxA autophosphorylates on a conserved histidine residue (H), using ATP as its phosphoryl donor. Phospho-CpxA then acts as a phosphoryl donor to the response regulator CpxR, which autophosphorylates on the conserved aspartate residue (D51). By homology to OmpR, phosphorylation of CpxR is predicted to expose the DNA-binding domain, thus promoting the binding of CpxR to its target genes (Pogliano et al., 1997, De Wulf et al., 2002).