OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain.
Transmembrane signaling between intracellular compartments is often controlled by regulated proteolysis. Escherichia coli respond to misfolded or unfolded outer-membrane porins (OMPs) in the periplasm by inducing sigma(E)-dependent transcription of stress genes in the cytoplasm. This process requires a proteolytic cascade initiated by the DegS protease, which destroys a transmembrane protein (RseA) that normally binds to and inhibits sigma(E). Here, we show that peptides ending with OMP-like C-terminal sequences bind the DegS PDZ domain, activate DegS cleavage of RseA, and induce sigma(E)-dependent transcription. These results suggest that DegS acts as a sensor of envelope stress by binding unassembled OMPs. DegS activation involves relief of inhibitory interactions between its PDZ and protease domains. Peptide binding to inhibitory PDZ domains in proteases related to DegS, including DegP/HtrA, may also regulate the degradation of specific substrates by these enzymes.
Walsh
Nathan P
NP
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Alba
Benjamin M
BM
Bose
Baundauna
B
Gross
Carol A
CA
Sauer
Robert T
RT
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019897:Periplasm / Q000201:enzymology; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D001426:Bacterial Proteins; C066496:DegS protein, Bacteria; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D018272:Porins; C433802:RseA protein, E coli; D012808:Sigma Factor; D014157:Transcription Factors; C489349:degS protein, Escherichia coli; C063202:sporulation-specific sigma factors