Local unfolding of the HSP27 monomer regulates chaperone activity
Local unfolding of the HSP27 monomer regulates chaperone activity
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HSP27 单体的局部解折叠调节伴侣活性
DOI：
10.1101/345751
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Alderson T
中科院分区：
文献类型：
--
作者：
Alderson T
小热休克蛋白 HSP27 是一种氧化还原敏感分子伴侣，在人体各处表达。在这里，我们描述了氧化还原诱导的 HSP27 及其保守的 α-晶状体蛋白结构域 (ACD) 的结构、动力学和功能的变化。当 HSP27 组装成寡聚体时，我们发现还原形成的单体在体外是高活性的伴侣，但容易发生自聚集。通过使用弛豫色散和高压核磁共振（NMR）光谱，我们观察到介导二聚化的一对β链在单体中部分展开。我们注意到，许多与遗传性神经病相关的 HSP27 突变聚集在这个动态区域。哺乳动物 sHSP 的 ACD 中的高水平序列保守性表明，游离单体或寡聚亚基中存在的暴露的无序界面可能是 sHSP 的一般功能特征。
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.