Article abstract
Nature Structural & Molecular Biology 15, 641 - 650 (2008)
Published online: 18 May 2008 | doi:10.1038/nsmb.1425
Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments
Tobias Haslberger1, Agnieszka Zdanowicz1,2, Ingo Brand1,3, Janine Kirstein4, Kürsad Turgay4, Axel Mogk1 & Bernd Bukau1
Abstract
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.
- Zentrum für Molekulare Biologie Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany.
- European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
- La Trobe University, Department of Biochemistry, Melbourne, Victoria 3086, Australia.
- Institut für Biologie-Mikrobiologie, Freie Universität Berlin, Königin-Luise-Strasse 12-16, 14195 Berlin, Germany.
Correspondence to: Axel Mogk1 e-mail: a.mogk@zmbh.uni-heidelberg.de
Correspondence to: Bernd Bukau1 e-mail: bukau@zmbh.uni-heidelberg.de
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