Abstract
Significance ClpB/Hsp100 chaperones protect cells from the devastating effects of protein inactivation and aggregation arising from extreme stress. This function is accomplished first by binding to the aggregates and then forcibly unraveling individual proteins by passing them through the central channel in the hexameric chaperones. Here, we investigate the role of the ClpB/Hsp100 N-terminal domain (NTD) in protein disaggregation. Our results demonstrate that ClpB recognizes exposed hydrophobic stretches in unfolded or aggregated client proteins via a substrate-binding groove in its NTD. We further show that the NTD has regulatory roles that include blocking the translocation channel in the absence of substrate and destabilizing client proteins upon binding, thus priming them for subsequent unfolding and disaggregation.
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Dates
Type | When |
---|---|
Created | 9 years, 8 months ago (Nov. 30, 2015, 11:15 p.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 12:42 a.m.) |
Indexed | 4 weeks ago (Aug. 2, 2025, 1:26 a.m.) |
Issued | 9 years, 9 months ago (Nov. 30, 2015) |
Published | 9 years, 9 months ago (Nov. 30, 2015) |
Published Online | 9 years, 9 months ago (Nov. 30, 2015) |
Published Print | 9 years, 8 months ago (Dec. 15, 2015) |
Funders
2
Gouvernement du Canada | Canadian Institutes of Health Research
10.13039/501100000024
Canadian Institutes of Health ResearchRegion: Americas
gov (National government)
Labels
6
- Instituts de Recherche en Santé du Canada
- Canadian Institutes of Health Research (CIHR)
- CIHR_IRSC
- Canadian Institutes of Health Research | Ottawa ON
- CIHR
- IRSC
Awards
1
- 404101
Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada
10.13039/501100000038
Natural Sciences and Engineering Research Council of CanadaRegion: Americas
gov (National government)
Labels
3
- Conseil de Recherches en Sciences Naturelles et en Génie du Canada
- NSERC
- CRSNG
Awards
1
- 455908
@article{Rosenzweig_2015, title={ClpB N-terminal domain plays a regulatory role in protein disaggregation}, volume={112}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1512783112}, DOI={10.1073/pnas.1512783112}, number={50}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Rosenzweig, Rina and Farber, Patrick and Velyvis, Algirdas and Rennella, Enrico and Latham, Michael P. and Kay, Lewis E.}, year={2015}, month=nov }