Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Alderson, TR; Roche, J; Gastall, HY; Dias, DM; Pritišanac, I; Ying, J; Bax, A; Benesch, JLP; Baldwin, AJ.
Local unfolding of the HSP27 monomer regulates chaperone activity.
Nat Commun. 2019; 10(1):1068
Doi: 10.1038/s41467-019-08557-8
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- Führende Autor*innen der Med Uni Graz
- Alderson Thomas Reid
- Co-Autor*innen der Med Uni Graz
- Pritisanac Iva
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- HSP27 Heat-Shock Proteins - chemistry, genetics, metabolism
- Heat-Shock Proteins - administration & dosage
- Molecular Chaperones - administration & dosage
- Mutation - administration & dosage
- Nuclear Magnetic Resonance, Biomolecular - administration & dosage
- Oxidation-Reduction - administration & dosage
- Peripheral Nervous System Diseases - genetics
- Protein Aggregation, Pathological - genetics
- Protein Conformation, beta-Strand - genetics
- Protein Multimerization - genetics
- Protein Structure, Quaternary - physiology
- Protein Unfolding - administration & dosage
- Recombinant Proteins - chemistry, genetics, metabolism