Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments
| Autor: | Axel Mogk, Janine Kirstein, Bernd Bukau, Agnieszka Zdanowicz, Ingo Brand, Kürşad Turgay, Tobias Haslberger |
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| Rok vydání: | 2007 |
| Předmět: |
Protein Folding
biology Escherichia coli Proteins Protein Renaturation Endopeptidase Clp Fusion protein Biochemistry Bacterial Proteins Structural Biology Heat shock protein Chaperone (protein) biological sciences Biophysics biology.protein Moiety Protein folding HSP70 Heat-Shock Proteins Threading (protein sequence) Cloning Molecular CLPB Molecular Biology Heat-Shock Proteins Molecular Chaperones |
| Zdroj: | Nature structuralmolecular biology. 15(6) |
| ISSN: | 1545-9985 |
| Popis: | The ring-forming AAA+ chaperone ClpB cooperates with the DnaK chaperone system to reactivate aggregated proteins. With the assistance of DnaK, ClpB extracts unfolded polypeptides from aggregates via substrate threading through its central channel. Here we analyze the processing of mixed aggregates consisting of protein fusions of misfolded and native domains. ClpB-DnaK reactivated all aggregated fusion proteins with similar efficiency, without unfolding native domains, demonstrating that partial threading of the misfolded moiety is sufficient to solubilize aggregates. Reactivation by ClpB-DnaK occurred even when two stably folded domains flanked the aggregated moiety, indicating threading of internal substrate segments. In contrast with the related AAA+ chaperone ClpC, ClpB lacks a robust unfolding activity, enabling it to sense the conformational state of substrates. ClpB rings are highly unstable, which may facilitate dissociation from trapped substrates during threading. |
| Databáze: | OpenAIRE |
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