Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments
- PMID: 18488042
- DOI: 10.1038/nsmb.1425
Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments
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.
Similar articles
-
Novel insights into the mechanism of chaperone-assisted protein disaggregation.Biol Chem. 2005 Aug;386(8):739-44. doi: 10.1515/BC.2005.086. Biol Chem. 2005. PMID: 16201868 Review.
-
M domains couple the ClpB threading motor with the DnaK chaperone activity.Mol Cell. 2007 Jan 26;25(2):247-60. doi: 10.1016/j.molcel.2006.11.008. Mol Cell. 2007. PMID: 17244532
-
Common and specific mechanisms of AAA+ proteins involved in protein quality control.Biochem Soc Trans. 2008 Feb;36(Pt 1):120-5. doi: 10.1042/BST0360120. Biochem Soc Trans. 2008. PMID: 18208398 Review.
-
The ClpB/Hsp104 molecular chaperone-a protein disaggregating machine.J Struct Biol. 2004 Apr-May;146(1-2):99-105. doi: 10.1016/j.jsb.2003.11.016. J Struct Biol. 2004. PMID: 15037241 Review.
-
Towards a unifying mechanism for ClpB/Hsp104-mediated protein disaggregation and prion propagation.Biochem Cell Biol. 2010 Feb;88(1):63-75. doi: 10.1139/o09-118. Biochem Cell Biol. 2010. PMID: 20130680 Review.
Cited by
-
Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation.Front Mol Biosci. 2015 May 19;2:22. doi: 10.3389/fmolb.2015.00022. eCollection 2015. Front Mol Biosci. 2015. PMID: 26042222 Free PMC article. Review.
-
Motor mechanism for protein threading through Hsp104.Mol Cell. 2009 Apr 10;34(1):81-92. doi: 10.1016/j.molcel.2009.02.026. Mol Cell. 2009. PMID: 19362537 Free PMC article.
-
Dynamic structural states of ClpB involved in its disaggregation function.Nat Commun. 2018 Jun 1;9(1):2147. doi: 10.1038/s41467-018-04587-w. Nat Commun. 2018. PMID: 29858573 Free PMC article.
-
Spiraling in Control: Structures and Mechanisms of the Hsp104 Disaggregase.Cold Spring Harb Perspect Biol. 2019 Aug 1;11(8):a034033. doi: 10.1101/cshperspect.a034033. Cold Spring Harb Perspect Biol. 2019. PMID: 30745294 Free PMC article. Review.
-
The Impact of Hidden Structure on Aggregate Disassembly by Molecular Chaperones.Front Mol Biosci. 2022 Jul 7;9:915307. doi: 10.3389/fmolb.2022.915307. eCollection 2022. Front Mol Biosci. 2022. PMID: 35874607 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
