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

References listed in PDB file

Key reference

• Title: A conserved activation cluster is required for allosteric communication in htra-Family proteases.
• Authors: A.K.De regt, S.Kim, J.Sohn, R.A.Grant, T.A.Baker, R.T.Sauer.
• Ref.: Structure, 2015, 23, 517-526. [DOI no: 10.1016/j.str.2015.01.012]
• PubMed id: 25703375

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.