Inhibition of regulated proteolysis by RseB.

The Escherichia coli envelope-stress response is a sensor system that increases transcription of stress genes in the cytoplasm when misfolded porins are detected in the periplasm. This response is initiated by DegS cleavage of the periplasmic domain of RseA, a transmembrane protein. Additional proteolysis of transmembrane and cytoplasmic portions of RseA then frees the sigma(E) transcription factor, which directs the transcriptional response. We show that RseB protein, a known negative regulator, inhibits proteolysis by DegS in vitro by binding tightly to the periplasmic domain of RseA. Inhibition of DegS cleavage requires RseB binding to a conserved region near the C terminus of the poorly structured RseA domain, but the RseA sequences that mediate DegS recognition and RseB binding do not overlap directly. Although DegS cleavage of RseA is normally activated by binding of the C termini of porins to the PDZ domain of DegS, RseB inhibition is independent of this activation mechanism.