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PDBsum entry 3mh4
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References listed in PDB file
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Key reference
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Title
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Htra proteases have a conserved activation mechanism that can be triggered by distinct molecular cues.
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Authors
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T.Krojer,
J.Sawa,
R.Huber,
T.Clausen.
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Ref.
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Nat Struct Biol, 2010,
17,
844-852.
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PubMed id
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Abstract
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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.
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