PDBsum entry 2r3y

Hydrolase/hydrolase activator

PDB id: 2r3y

Contents

Protein chains

280 a.a. *

Ligands

VAL-TYR-TRP-PHE ×3

Waters ×157

* Residue conservation analysis

PDB id:

2r3y

Name:

Hydrolase/hydrolase activator

Title:

Crystal structure of the degs protease in complex with the ywf activating peptide

Structure:

Protease degs. Chain: a, b, c. Engineered: yes. Synthetic peptide ywf. Chain: d, e, f. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: degs, hhob, htrh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the ywf peptide mimics thE C-terminus of outer membrane proteins.

Resolution:

2.50Å R-factor: 0.204 R-free: 0.234

Authors:

T.Clausen,H.Hasselblatt

Key ref:

H.Hasselblatt et al. (2007). 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. PubMed id: 17938245

Date:

30-Aug-07 Release date: 27-Nov-07

Protein chains

P0AEE3  (DEGS_ECOLI) -  Serine endoprotease DegS from Escherichia coli (strain K12)

Seq: 355 a.a.

Struc: 280 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.21.107 - peptidase Do.

Genes Dev 21:2659-2670 (2007)

PubMed id: 17938245

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.

H.Hasselblatt, R.Kurzbauer, C.Wilken, T.Krojer, J.Sawa, J.Kurt, R.Kirk, S.Hasenbein, M.Ehrmann, T.Clausen.

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.