PDBsum entry 4rqz

Hydrolase/peptide

PDB id: 4rqz

Contents

Protein chains

272 a.a.

274 a.a.

Ligands

TYR-GLN-PHE ×2

VAL-TYR-GLN-PHE

Waters ×255

PDB id:

4rqz

Name:

Hydrolase/peptide

Title:

Re-refinement of 1soz, crystal structure of degs protease in complex with an activating peptide

Structure:

Protease degs. Chain: a, b, c. Fragment: protease and pdz domains. Engineered: yes. Activating peptide. Chain: d, e, f. Fragment: synthetic activating peptide. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: degs, p12b_c3347. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide

Resolution:

2.40Å R-factor: 0.198 R-free: 0.226

Authors:

R.T.Sauer,R.A.Grant

Key ref:

A.K.de Regt et al. (2015). A conserved activation cluster is required for allosteric communication in HtrA-family proteases. Structure, 23, 517-526. PubMed id: 25703375 DOI: 10.1016/j.str.2015.01.012

Date:

05-Nov-14 Release date: 11-Mar-15

Protein chain

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

Seq: 355 a.a.

Struc: 272 a.a.*

Protein chains

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

Seq: 355 a.a.

Struc: 274 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.3.4.21.107 - peptidase Do.

DOI no: 10.1016/j.str.2015.01.012

Structure 23:517-526 (2015)

PubMed id: 25703375

A conserved activation cluster is required for allosteric communication in HtrA-family proteases.

A.K.de Regt, S.Kim, J.Sohn, R.A.Grant, T.A.Baker, R.T.Sauer.

ABSTRACT

In E. coli, outer-membrane stress causes a transcriptional response through a signaling cascade initiated by DegS cleavage of a transmembrane antisigma factor. Each subunit of DegS, an HtrA-family protease, contains a protease domain and a PDZ domain. The trimeric protease domain is autoinhibited by the unliganded PDZ domains. Allosteric activation requires binding of unassembled outer-membrane proteins (OMPs) to the PDZ domains and protein substrate binding. Here, we identify a set of DegS residues that cluster together at subunit-subunit interfaces in the trimer, link the active sites and substrate binding sites, and are crucial for stabilizing the active enzyme conformation in response to OMP signaling. These residues are conserved across the HtrA-protease family, including orthologs linked to human disease, supporting a common mechanism of allosteric activation. Indeed, mutation of residues at homologous positions in the DegP quality-control protease also eliminates allosteric activation.