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Local unfolding of the HSP27 monomer regulates chaperone activity
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). While HSP27 assembles into oligomers, we sho...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403371/ https://www.ncbi.nlm.nih.gov/pubmed/30842409 http://dx.doi.org/10.1038/s41467-019-08557-8 |
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author | Alderson, T. Reid Roche, Julien Gastall, Heidi Y. Dias, David M. Pritišanac, Iva Ying, Jinfa Bax, Ad Benesch, Justin L. P. Baldwin, Andrew J. |
author_facet | Alderson, T. Reid Roche, Julien Gastall, Heidi Y. Dias, David M. Pritišanac, Iva Ying, Jinfa Bax, Ad Benesch, Justin L. P. Baldwin, Andrew J. |
author_sort | Alderson, T. Reid |
collection | PubMed |
description | 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). While HSP27 assembles into oligomers, we show that the monomers formed upon reduction are highly active chaperones in vitro, but are susceptible to self-aggregation. By using relaxation dispersion and high-pressure nuclear magnetic resonance (NMR) spectroscopy, we observe that the pair of β-strands that mediate dimerisation partially unfold in the monomer. We note that numerous HSP27 mutations associated with inherited neuropathies cluster to this dynamic region. High levels of sequence conservation in ACDs from mammalian sHSPs suggest that the exposed, disordered interface present in free monomers or oligomeric subunits may be a general, functional feature of sHSPs. |
format | Online Article Text |
id | pubmed-6403371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64033712019-03-08 Local unfolding of the HSP27 monomer regulates chaperone activity Alderson, T. Reid Roche, Julien Gastall, Heidi Y. Dias, David M. Pritišanac, Iva Ying, Jinfa Bax, Ad Benesch, Justin L. P. Baldwin, Andrew J. Nat Commun Article 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). While HSP27 assembles into oligomers, we show that the monomers formed upon reduction are highly active chaperones in vitro, but are susceptible to self-aggregation. By using relaxation dispersion and high-pressure nuclear magnetic resonance (NMR) spectroscopy, we observe that the pair of β-strands that mediate dimerisation partially unfold in the monomer. We note that numerous HSP27 mutations associated with inherited neuropathies cluster to this dynamic region. High levels of sequence conservation in ACDs from mammalian sHSPs suggest that the exposed, disordered interface present in free monomers or oligomeric subunits may be a general, functional feature of sHSPs. Nature Publishing Group UK 2019-03-06 /pmc/articles/PMC6403371/ /pubmed/30842409 http://dx.doi.org/10.1038/s41467-019-08557-8 Text en © The Author(s) 2019 Open Access 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/. |
spellingShingle | Article Alderson, T. Reid Roche, Julien Gastall, Heidi Y. Dias, David M. Pritišanac, Iva Ying, Jinfa Bax, Ad Benesch, Justin L. P. Baldwin, Andrew J. Local unfolding of the HSP27 monomer regulates chaperone activity |
title | Local unfolding of the HSP27 monomer regulates chaperone activity |
title_full | Local unfolding of the HSP27 monomer regulates chaperone activity |
title_fullStr | Local unfolding of the HSP27 monomer regulates chaperone activity |
title_full_unstemmed | Local unfolding of the HSP27 monomer regulates chaperone activity |
title_short | Local unfolding of the HSP27 monomer regulates chaperone activity |
title_sort | local unfolding of the hsp27 monomer regulates chaperone activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403371/ https://www.ncbi.nlm.nih.gov/pubmed/30842409 http://dx.doi.org/10.1038/s41467-019-08557-8 |
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