Journal article
Local unfolding of the HSP27 monomer regulates chaperone activity
- Abstract:
- The small heat-shock protein HSP27 is a redox-sensitive molecular chaperone that is expressed throughout the human body. Here we describe redox-induced changes to the structure, dynamics, and function of HSP27 and its conserved α-crystallin domain (ACD), and provide the first structural characterization of a small heat-shock protein monomer using nuclear magnetic resonance (NMR) spectroscopy. While HSP27 assembles into oligomers, we show that the transiently populated monomers that are released upon reduction are highly active chaperones in vitro, but are kinetically unstable and susceptible to uncontrolled self-aggregation. By using relaxation dispersion and high-pressure NMR spectroscopy, we observe that the pair of β-strands that mediate dimerization partially unfold in the monomer. Strikingly, we note that numerous HSP27 mutations associated with inherited neuropathies cluster to this dynamic region. The high degree of sequence conservation in the ACD amongst mammalian sHSPs suggests that the exposed, disordered interface within the context of oligomers or free in solution may be a general, functional feature of these molecular chaperones.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.4MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-019-08557-8
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 10
- Article number:
- 1068
- Publication date:
- 2019-03-06
- Acceptance date:
- 2019-01-05
- DOI:
- EISSN:
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2041-1723
- Keywords:
- Pubs id:
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pubs:965607
- UUID:
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uuid:d2a68ded-19e8-4498-97a2-85c01d542ed1
- Local pid:
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pubs:965607
- Source identifiers:
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965607
- Deposit date:
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2019-01-22
Terms of use
- Copyright holder:
- Alderson et al
- Copyright date:
- 2019
- Notes:
- © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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