2R3Y

Crystal structure of the DegS protease in complex with the YWF activating peptide

Summary for 2R3Y

• Entry DOI: 10.2210/pdb2r3y/pdb
• Related: 1sot 1soz 1vcw 2r3u
• Descriptor: Protease degS, Synthetic peptide YWF (3 entities in total)
• Functional Keywords: reversible activation of a protease, catalytic triad, hydrolase, periplasm, serine protease, hydrolase-hydrolase activator complex, hydrolase/hydrolase activator
• Biological source: Escherichia coli; More
• Cellular location: Periplasm (Potential): P0AEE3
• Total number of polymer chains: 6
• Total formula weight: 103581.36

Authors

Clausen, T.,Hasselblatt, H. (deposition date: 2007-08-30, release date: 2007-11-27, Last modification date: 2023-08-30)

Primary citation

Hasselblatt, H.,Kurzbauer, R.,Wilken, C.,Krojer, T.,Sawa, J.,Kurt, J.,Kirk, R.,Hasenbein, S.,Ehrmann, M.,Clausen, T.
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.
Genes Dev., 21:2659-2670, 2007

PubMed Abstract: The unfolded protein response of Escherichia coli is triggered by the accumulation of unassembled outer membrane proteins (OMPs) in the cellular envelope. The PDZ-protease DegS recognizes these mislocalized OMPs and initiates a proteolytic cascade that ultimately leads to the sigmaE-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly. The general features of how OMPs activate the protease function of DegS have not yet been systematically addressed. Furthermore, it is unknown how the PDZ domain keeps the protease inactive in the resting state, which is of crucial importance for the functioning of the entire sigmaE stress response. Here we show in atomic detail how DegS is able to integrate the information of distinct stress signals that originate from different OMPs containing a -x-Phe C-terminal motif. A dedicated loop of the protease domain, loop L3, serves as a versatile sensor for allosteric ligands. L3 is capable of interacting differently with ligands but reorients in a conserved manner to activate DegS. Our data also indicate that the PDZ domain directly inhibits protease function in the absence of stress signals by wedging loop L3 in a conformation that ultimately disrupts the proteolytic site. Thus, the PDZ domain and loop L3 of DegS define a novel molecular switch allowing strict regulation of the sigmaE stress response system.

PubMed: 17938245
DOI: 10.1101/gad.445307

Experimental method

X-RAY DIFFRACTION (2.5 Å)