Sensing Stress between the Membranes

Abstract

The periplasm (the space between the inner and outer membranes of bacteria) is the site of activation of the periplasmic stress response. Like the cytosolic stress response and the eukaryotic endoplasmic and cytosolic stress responses, unfolded proteins trigger a transcriptional activation profile that allows cells to produce more chaperones and protein-folding agents (see Young and Hartl). Although, the periplasmic stress response is fairly well characterized, the sensor that initiates the process has remained elusive. The response consists of activation of the protease DegS, which cleaves transmembrane protein RseA, which then releases the transcription factor σ E to allow the activation of stress response genes. Walsh et al. show that DegS is inhibited by its PDZ domain and that binding of the PDZ domain toYQF motifs of outer membrane protein porins activates the protease. Bacteria expressing DegS lacking the PDZ domain showed increased σ E activity. Using an oriented peptide library, a preferred binding sequence for the PDZ domain was identified (YXF/M-COOH), and examination of the sequences of outer membrane proteins showed that several proteins terminated in these sequences. Expression of an OmpC (an outer membrane porin) COOH-terminal fragment containing the YQF motif, stimulated σ E activity, but only in cells expressing the wild-type DegS, not in cells expressing the PDZ-lacking DegS mutant. In vitro RseA was cleaved by DegS in the presence of YXF-COOH peptides. Thus, stress such as heat would promote unfolding of the porins exposing the YXF-COOH sequences that would interact with the PDZ domain of DegS and alleviate repression of the protease activity. Thus, DegS is both the sensor and the first executor of the periplasmic stress response. J. C. Young, F. U. Hartl, A stress sensor for the bacterial periplasm. Cell 113 , 1-4 (2003) [Online Journal] N. P. Walsh, B. M. Alba, B. Bose, C. A. Gross, R. T. Sauer, OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain. Cell 113 , 61-71 (2003). [Online Journal]