Local unfolding of the HSP27 monomer regulates chaperone activity

T Reid Alderson; Julien Roche; Heidi Y Gastall; David M Dias; Iva Pritišanac; Jinfa Ying; Ad Bax; Justin L P Benesch; Andrew J Baldwin

doi:10.1038/s41467-019-08557-8

Retour

Local unfolding of the HSP27 monomer regulates chaperone activity

Article de revue

Avec comité de lecture

Local unfolding of the HSP27 monomer regulates chaperone activity

T Reid Alderson, Julien Roche, Heidi Y Gastall, David M Dias, Iva Pritišanac, Jinfa Ying, Ad Bax, Justin L P Benesch et Andrew J Baldwin

Nature communications, Vol.10(1), pp.1068-16

06/03/2019

DOI: https://doi.org/10.1038/s41467-019-08557-8

PMID: 30842409

Résumé

HSP27 Heat-Shock Proteins - chemistry

HSP27 Heat-Shock Proteins - genetics

HSP27 Heat-Shock Proteins - metabolism

Mutation

Nuclear Magnetic Resonance, Biomolecular

Oxidation-Reduction

Peripheral Nervous System Diseases - genetics

Protein Aggregation, Pathological - genetics

Protein Conformation, beta-Strand - genetics

Protein Multimerization - genetics

Protein Structure, Quaternary - physiology

Protein Unfolding

Recombinant Proteins - chemistry

Recombinant Proteins - genetics

Recombinant Proteins - metabolism

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.

Indicateurs

1 Consultations de la notice

See more details

Détails

Titre: Local unfolding of the HSP27 monomer regulates chaperone activity
Créateurs - sans rôle: T Reid Alderson - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
Julien Roche - Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA
Heidi Y Gastall - Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK
David M Dias - Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK
Iva Pritišanac - Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK
Jinfa Ying - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
Ad Bax - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
Justin L P Benesch - Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK. justin.benesch@chem.ox.ac.uk
Andrew J Baldwin - Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK. andrew.baldwin@chem.ox.ac.uk
Détails de publication: Nature communications, Vol.10(1), pp.1068-16
Identifiants: 99141270509311
Unité académique: Institut de Recherche en Cancérologie de Montpellier - IRCM
Langue: English
Type de ressource: Journal article