Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK.
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2019 Mar 6;10(1):1068. doi: 10.1038/s41467-019-08557-8.
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.
小分子热休克蛋白 HSP27 是一种氧化还原敏感的分子伴侣，在人体全身表达。在这里，我们描述了 HSP27 及其保守的 α-晶体蛋白结构域（ACD）的结构、动态和功能的氧化还原诱导变化。虽然 HSP27 组装成寡聚物，但我们表明还原形成的单体在体外是高度活跃的伴侣，但容易自聚集。通过使用弛豫分散和高压核磁共振（NMR）光谱，我们观察到介导二聚化的β-链对在单体中部分展开。我们注意到与遗传性神经病相关的许多 HSP27 突变聚集在这个动态区域。哺乳动物 sHSPs 的 ACD 中高度的序列保守性表明，在游离单体或寡聚亚基中存在的暴露的、无规的界面可能是 sHSPs 的一般功能特征。
