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Concurrent chaperone and protease activities of ClpAP and the requirement for the N-terminal ClpA ATP binding site for chaperone activity
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By employing a chaperone-defective ClpA molecule, which is able to exert this activity only upon association with ClpP, the authors present evidence that the ClpAP holocomplex is able to exert both a proteolytic and protein-remodeling function
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Pak M, Hoskins JR, Singh SK, Maurizi MR, Wickner S Concurrent chaperone and protease activities of ClpAP and the requirement for the N-terminal ClpA ATP binding site for chaperone activity. J Biol Chem. 274:1999;19316-19322. By employing a chaperone-defective ClpA molecule, which is able to exert this activity only upon association with ClpP, the authors present evidence that the ClpAP holocomplex is able to exert both a proteolytic and protein-remodeling function.
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In this study, a chaperone-like activity of the eukaryotic proteasome was demonstrated for the model substrate citrate synthase. The non-native molecule binds to the base subassembly. It is released in a folding-competent state in an ATP-stimulated process
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Braun B, Glickman M, Kraft R, Dahlmann B, Kloetzel P-M, Finley D, Schmidt M The base of the proteasome regulatory particle exhibits chaperone-like activity. Nat Cell Biol. 1:1999;221-226. In this study, a chaperone-like activity of the eukaryotic proteasome was demonstrated for the model substrate citrate synthase. The non-native molecule binds to the base subassembly. It is released in a folding-competent state in an ATP-stimulated process.
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The 19S regulatory complex of the proteasome functions independently of proteolysis in nucleotide excision repair
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Rad 23 is a mediator of nucleotide excision repair that was previously demonstrated to associate with the proteasome via a ubiquitin-like domain at its amino-terminus. This paper shows that the Rad23-proteasome interaction is important for nucleotide excision repair in vitro. The data also suggest for the first time a non-proteolytic activity of the proteasome, which is suggested to be a chaperone activity
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Russell SJ, Reed SH, Huang W, Friedberg EC, Johnston SA The 19S regulatory complex of the proteasome functions independently of proteolysis in nucleotide excision repair. Molec Cell. 3:1999;687-695. Rad 23 is a mediator of nucleotide excision repair that was previously demonstrated to associate with the proteasome via a ubiquitin-like domain at its amino-terminus. This paper shows that the Rad23-proteasome interaction is important for nucleotide excision repair in vitro. The data also suggest for the first time a non-proteolytic activity of the proteasome, which is suggested to be a chaperone activity.
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This study provides the first direct evidence for an active unfolding event in a chaperone-mediated refolding system. By analyzing the velocity of hydrogen exchange of tritium-labeled protein, it was demonstrated that protected protons become accessible to the surrounding medium during Rubisco refolding in the presence of the complete chaperonin system
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Shtilerman M, Lorimer GH, Englander SW Chaperonin function: folding by forced unfolding. Science. 284:1999;822-825. This study provides the first direct evidence for an active unfolding event in a chaperone-mediated refolding system. By analyzing the velocity of hydrogen exchange of tritium-labeled protein, it was demonstrated that protected protons become accessible to the surrounding medium during Rubisco refolding in the presence of the complete chaperonin system.
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FtsH is a membrane-inserted ATP-dependent protease with its functional domains facing the cytoplasm. Despite this topology, FtsH is able to degrade a membrane-bound protein that is exposed to the periplasmic space. Complete degradation by FtsH is only possible if disulfide bond formation in the periplasm is prevented. Presumably the disulfide bonds impose a steric block to the unfolding and pulling forces imposed by FtsH during the degradation process
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Kihara A, Akiyama Y, Ito K Dislocation of membrane proteins in FtsH-mediated proteolysis. EMBO J. 18:1999;2970-2981. FtsH is a membrane-inserted ATP-dependent protease with its functional domains facing the cytoplasm. Despite this topology, FtsH is able to degrade a membrane-bound protein that is exposed to the periplasmic space. Complete degradation by FtsH is only possible if disulfide bond formation in the periplasm is prevented. Presumably the disulfide bonds impose a steric block to the unfolding and pulling forces imposed by FtsH during the degradation process.
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The authors show that the proteasome plays a key role in the extraction of membrane proteins from the ER membrane prior to their degradation. Data obtained with proteasome mutants suggest that the driving force for retrograde protein transport from the ER may be generated by the proteasome
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Mayer TU, Braun T, Jentsch S Role of the proteasome in membrane extraction of a short-lived ER-transmembrane protein. EMBO J. 17:1998;3251-3257. The authors show that the proteasome plays a key role in the extraction of membrane proteins from the ER membrane prior to their degradation. Data obtained with proteasome mutants suggest that the driving force for retrograde protein transport from the ER may be generated by the proteasome.
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