3MH6

HtrA proteases are activated by a conserved mechanism that can be triggered by distinct molecular cues

Summary for 3MH6

• Entry DOI: 10.2210/pdb3mh6/pdb
• Related: 3MH4 3MH5 3MH7
• Descriptor: Protease do, DIISOPROPYL PHOSPHONATE (2 entities in total)
• Functional Keywords: degp, htra, protease, hydrolase
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Peripheral membrane protein; Cytoplasmic side: P0C0V0
• Total number of polymer chains: 1
• Total formula weight: 48108.22

Authors

Krojer, T.,Sawa, J.,Huber, R.,Clausen, T. (deposition date: 2010-04-07, release date: 2010-06-30, Last modification date: 2024-10-30)

Primary citation

Krojer, T.,Sawa, J.,Huber, R.,Clausen, T.
HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues
Nat.Struct.Mol.Biol., 17:844-852, 2010

PubMed Abstract: 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.

PubMed: 20581825
DOI: 10.1038/nsmb.1840

Experimental method

X-RAY DIFFRACTION (3.6 Å)