Specificity and structural characterization of the PDZ domain from DegS, an extracytoplasmic E. coli protease

Abstract

DegS is a membrane-bound bacterial protease that is involved in the extracytoplasmic-stress response. The C-terminal domain has limited homology to PDZ domains and was thought to be involved in regulation or substrate recognition. A model of this PDZ domain was generated from NMR solution studies and homology modeling. Peptide selection studies identified the sequence Tyr-Tyr-Phe (YYF) as a C-terminal motif that binds to the PDZ domain. Possible targets were identified including many of the outer-membrane proteins (OMPs), which contain both a conserved terminal YxF and internal YYF sequences. The binding of the DegS PDZ domain to a YYF peptide and OMP derivatives were confirmed using microcalorimetry. Because stress signaling can be triggered by over-expression of some of the outer-membrane proteins, I propose that DegS may receive a signal from unassembled OMPs and transmit it to the aE transcription factor by increasing proteolysis of RseA.