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Title
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Structural basis for the regulated protease and chaperone function of DegP.
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Authors
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T.Krojer,
J.Sawa,
E.Schäfer,
H.R.Saibil,
M.Ehrmann,
T.Clausen.
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Ref.
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Nature, 2008,
453,
885-890.
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PubMed id
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Abstract
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All organisms have to monitor the folding state of cellular proteins precisely.
The heat-shock protein DegP is a protein quality control factor in the bacterial
envelope that is involved in eliminating misfolded proteins and in the
biogenesis of outer-membrane proteins. Here we describe the molecular mechanisms
underlying the regulated protease and chaperone function of DegP from
Escherichia coli. We show that binding of misfolded proteins transforms
hexameric DegP into large, catalytically active 12-meric and 24-meric multimers.
A structural analysis of these particles revealed that DegP represents a protein
packaging device whose central compartment is adaptable to the size and
concentration of substrate. Moreover, the inner cavity serves antagonistic
functions. Whereas the encapsulation of folded protomers of outer-membrane
proteins is protective and might allow safe transit through the periplasm,
misfolded proteins are eliminated in the molecular reaction chamber. Oligomer
reassembly and concomitant activation on substrate binding may also be critical
in regulating other HtrA proteases implicated in protein-folding diseases.
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