Allosteric Activation of DegS, a Stress Sensor PDZ Protease

Jungsan Sohn, Robert A. Grant, Robert T. Sauer

Research output: Contribution to journalArticle

Abstract

Regulated intramembrane proteolysis is a method for transducing signals between cellular compartments. When protein folding is compromised in the periplasm of E. coli, the C termini of outer-membrane proteins (OMPs) bind to the PDZ domains of the trimeric DegS protease and activate cleavage of RseA, a transmembrane transcriptional regulator. We show here that DegS is an allosteric enzyme. OMP binding shifts the equilibrium from a nonfunctional state, in which the active sites are unreactive, to the functional proteolytic conformation. 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. OMP-induced activation and RseA binding are both positively cooperative, allowing switch-like behavior of the OMP-DegS-RseA system. Residues involved in the DegS allosteric switch are conserved in the DegP/HtrA and HtrA2/Omi families, suggesting that many PDZ proteases use a common mechanism of allosteric activation.

Original languageEnglish (US)
Pages (from-to)572-583
Number of pages12
JournalCell
Volume131
Issue number3
DOIs
StatePublished - Nov 2 2007
Externally publishedYes

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PDZ Domains
Membrane Proteins
Peptide Hydrolases
Chemical activation
Protein Binding
Sensors
Conformations
Periplasm
Protein Folding
Switches
Proteolysis
Protein folding
Catalytic Domain
Escherichia coli
Enzymes
Experiments
OmpC protein

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Allosteric Activation of DegS, a Stress Sensor PDZ Protease. / Sohn, Jungsan; Grant, Robert A.; Sauer, Robert T.

In: Cell, Vol. 131, No. 3, 02.11.2007, p. 572-583.

Research output: Contribution to journalArticle

Sohn, Jungsan ; Grant, Robert A. ; Sauer, Robert T. / Allosteric Activation of DegS, a Stress Sensor PDZ Protease. In: Cell. 2007 ; Vol. 131, No. 3. pp. 572-583.
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