Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau.
Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau.
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DOI：
10.1038/s41467-018-07012-4
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发表时间：
2018-11-01
影响因子：
16.6
通讯作者：
Gestwicki JE
中科院分区：
文献类型：
--
作者：
Freilich R;Betegon M;Tse E;Mok SA;Julien O;Agard DA;Southworth DR;Takeuchi K;Gestwicki JE
小分子热休克蛋白(SHSP)是一类限制蛋白质聚集的寡聚分子伴侣。然而，人们通常不清楚sHSPs与其客户蛋白结合的位置，也不清楚这些蛋白质-蛋白质相互作用(PPI)是如何调节的。在这里，我们映射了人类Hsp27和微管相关蛋白tau(MAPT/tau)之间的PPI。我们发现，HSP27利用其α晶体蛋白结构域的保守的β4-β8裂解，选择性地识别tau的两个聚集倾向区域。β4-β8区域也是HSP27-HSP27相互作用的部位，这表明竞争性PPI可能是一个重要的调控范式。事实上，我们发现每个单独的PPI都相对较弱，对共享位点的竞争似乎同时控制了客户端结合和Hsp27寡聚。这些发现突显了多个竞争性PPI在HSP27功能中的重要性，并表明β4-β8凹槽对客户来说是一个可调的传感器。小分子热休克蛋白(SHSP)限制了tau等蛋白质的聚集。在这里，作者表明Hsp27识别tau的两个聚集倾向区域，这种相互作用与Hsp27寡聚竞争。
Small heat shock proteins (sHSPs) are a class of oligomeric molecular chaperones that limit protein aggregation. However, it is often not clear where sHSPs bind on their client proteins or how these protein-protein interactions (PPIs) are regulated. Here, we map the PPIs between human Hsp27 and the microtubule-associated protein tau (MAPT/tau). We find that Hsp27 selectively recognizes two aggregation-prone regions of tau, using the conserved β4-β8 cleft of its alpha-crystallin domain. The β4-β8 region is also the site of Hsp27–Hsp27 interactions, suggesting that competitive PPIs may be an important regulatory paradigm. Indeed, we find that each of the individual PPIs are relatively weak and that competition for shared sites seems to control both client binding and Hsp27 oligomerization. These findings highlight the importance of multiple, competitive PPIs in the function of Hsp27 and suggest that the β4-β8 groove acts as a tunable sensor for clients. Small heat shock proteins (sHSPs) limit the aggregation of proteins, such as tau. Here the authors show that Hsp27 recognizes two aggregation-prone regions of tau and that this interaction competes with Hsp27 oligomerization.
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