3MH5: Htra Proteases Are Activated By A Conserved Mechanism That Can Be Triggered By Distinct Molecular Cues

HtrA proteases are tightly regulated proteolytic assemblies that are essential for maintaining protein homeostasis in extracytosolic compartments. Though HtrA proteases have been characterized in detail, their precise molecular mechanism for switching between different functional states is still unknown. To address this, we carried out biochemical and structural studies of DegP from Escherichia coli. We show that effector-peptide binding to the PDZ domain of DegP induces oligomer conversion from resting hexameric DegP6 into proteolytically active 12-mers and 24-mers (DegP12/24). Moreover, our data demonstrate that a specific protease loop (L3) functions as a conserved molecular switch of HtrA proteases. L3 senses the activation signal-that is, the repositioned PDZ domain of substrate-engaged DegP12/24 or the binding of allosteric effectors to regulatory HtrA proteases such as DegS-and transmits this information to the active site. Implications for protein quality control and regulation of oligomeric enzymes are discussed.
PDB ID: 3MH5Download
MMDB ID: 83071
PDB Deposition Date: 2010/4/7
Updated in MMDB: 2010/07
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 3MH5: hexameric; determined by author
Molecular Components in 3MH5
Label Count Molecule
Proteins (6 molecules)
Protease DO(Gene symbol: degP)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB