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Local unfolding of the HSP27 monomer regulates chaperone activity

Author

Listed:
  • T. Reid Alderson

    (University of Oxford
    National Institutes of Health)

  • Julien Roche

    (National Institutes of Health
    Iowa State University)

  • Heidi Y. Gastall

    (University of Oxford)

  • David M. Dias

    (University of Oxford)

  • Iva Pritišanac

    (University of Oxford)

  • Jinfa Ying

    (National Institutes of Health)

  • Ad Bax

    (National Institutes of Health)

  • Justin L. P. Benesch

    (University of Oxford)

  • Andrew J. Baldwin

    (University of Oxford)

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). 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.

Suggested Citation

  • T. Reid Alderson & Julien Roche & Heidi Y. Gastall & David M. Dias & Iva Pritišanac & Jinfa Ying & Ad Bax & Justin L. P. Benesch & Andrew J. Baldwin, 2019. "Local unfolding of the HSP27 monomer regulates chaperone activity," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08557-8
    DOI: 10.1038/s41467-019-08557-8
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    Cited by:

    1. Charles Buchanan & Gogulan Karunanithy & Olga Tkachenko & Michael Barber & Michael T. Marty & Timothy J. Nott & Christina Redfield & Andrew J. Baldwin, 2025. "UnidecNMR: automatic peak detection for NMR spectra in 1-4 dimensions," Nature Communications, Nature, vol. 16(1), pages 1-11, December.

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