PMID:15978546
| Citation |
Hansen, J, Gregersen, N and Bross, P (2005) Differential degradation of variant medium-chain acyl-CoA dehydrogenase by the protein quality control proteases Lon and ClpXP. Biochem. Biophys. Res. Commun. 333:1160-70 |
|---|---|
| Abstract |
The coordinated activities of chaperones and proteases that supervise protein folding and degradation are important factors for deciding the fate of proteins whose folding is impaired by missense variations. We have studied the role of Lon and ClpXP proteases in handling of wild-type and a folding-impaired disease-associated variant (R28C) of the mitochondrial enzyme medium-chain acyl-CoA dehydrogenase (MCAD). Using an Escherichia coli model system, we co-overexpressed the MCAD variants and the respective proteases at two conditions: at 31 degrees C where R28C MCAD protein folds partially and at 37 degrees C where it misfolds and aggregates. Co-overexpression of Lon protease considerably accelerated the degradation rate of a pool of R28C variant MCAD synthesised during a 30min pulse and counteracted accumulation of aggregates at 37 degrees C, whereas increasing the amounts of ClpXP protease had no clear effect. Co-overexpression of either Lon or ClpXP protease markedly decreased the steady state levels of both wild-type and R28C mutant MCAD at 37 degrees C but not at 31 degrees C. Our results suggest that Lon is more efficient than ClpXP in elimination of non-native MCAD protein conformations, and accordingly, that Lon can recognise a broader spectrum of MCAD protein conformations. |
| Links |
PubMed Online version:10.1016/j.bbrc.2005.06.024 |
| Keywords |
Acyl-CoA Dehydrogenase/genetics; Acyl-CoA Dehydrogenase/metabolism; Biodegradation, Environmental; Endopeptidase Clp/genetics; Endopeptidase Clp/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Mitochondria/enzymology; Protease La/genetics; Protease La/metabolism; Protein Isoforms; Recombinant Proteins/metabolism |
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