OMP Peptide Signals Initiate the Envelope-Stress Response by Activating DegS Protease via Relief of Inhibition Mediated by Its PDZ Domain

@article{Walsh2003OMPPS,
  title={OMP Peptide Signals Initiate the Envelope-Stress Response by Activating DegS Protease via Relief of Inhibition Mediated by Its PDZ Domain},
  author={N. Walsh and B. M. Alba and Baundauna Bose and C. Gross and R. Sauer},
  journal={Cell},
  year={2003},
  volume={113},
  pages={61-71}
}
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… Expand
Steric clashes with bound OMP peptides activate the DegS stress-response protease
TLDR
It is shown that OMP peptides initiate a steric clash between the PDZ domain and the L3 loop that results in a structural rearrangement of the loop and breaking of autoinhibitory interactions, resulting in proteolytic activation of DegS by OMP-peptide binding. Expand
OMP peptides activate the DegS stress-sensor protease by a relief of inhibition mechanism.
TLDR
It is shown that an active-site DegS mutation partially bypasses the requirement for peptide activation and acts synergistically with mutations that disrupt contacts between the protease and PDZ domains, which support an allosteric model. Expand
Fine-tuning of the Escherichia coli sigmaE envelope stress response relies on multiple mechanisms to inhibit signal-independent proteolysis of the transmembrane anti-sigma factor, RseA.
TLDR
It is demonstrated that RseB, which binds to the periplasmic face of RseA, and DegS each independently inhibits RseP cleavage of intact RSEA, which makes this signal transduction system sensitive to a wide range of OMP concentrations and unresponsive to variations in the levels of DegS. Expand
OMP peptides modulate the activity of DegS protease by differential binding to active and inactive conformations.
TLDR
It is shown that DegS stimulation can be regulated by OMP peptide affinity for the active and for the inactive protease conformations, as well as by preferential substrate binding to active DegS, and an allosteric pathway that links peptide binding to DegS activation is suggested. Expand
Inhibition of regulated proteolysis by RseB
TLDR
RseB protein, a known negative regulator, inhibits proteolysis by DegS in vitro by binding tightly to the periplasmic domain of RseA, a transmembrane protein. Expand
Regulated proteolysis: control of the Escherichia coli σ(E)-dependent cell envelope stress response.
TLDR
The extensive physiological, biochemical, and structural studies on the σ(E) system are reviewed that provide remarkable insights into the mechanistic underpinnings of this regulated proteolytic signal transduction pathway. Expand
Signal integration by DegS and RseB governs the σE-mediated envelope stress response in Escherichia coli
TLDR
This work demonstrates that inactivation of a second negative regulator, the periplasmic protein RseB, is also required for σE induction in vivo and proposes that the use of an AND gate enables ρE to sense and integrate multivariate signals from the envelope. Expand
Regulation of the sigmaE stress response by DegS: how the PDZ domain keeps the protease inactive in the resting state and allows integration of different OMP-derived stress signals upon folding stress.
TLDR
This work shows in atomic detail how PDZ-protease DegS is able to integrate the information of distinct stress signals that originate from different OMPs containing a -x-Phe C-terminal motif, and defines a novel molecular switch allowing strict regulation of the sigmaE stress response system. Expand
Allosteric Activation of DegS, a Stress Sensor PDZ Protease
TLDR
Crystallographic, biochemical, and mutagenic experiments show that the unliganded PDZ domains are inhibitory and suggest that OMP binding per se is sufficient to stabilize the relaxed conformation and activate DegS, showing here that DegS is an allosteric enzyme. Expand
Two stress sensor proteins for the expression of sigmaE regulon: DegS and RseB
  • D. Kim
  • Biology, Medicine
  • Journal of Microbiology
  • 2015
TLDR
Interestingly, biogenesis of OMP and LPS appears to cross-talk with each other, indicating that dysfunction of either OMP or LPS can initiate RseA proteolysis, which regulates sigmaEdependent transcription. Expand
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