Chaperone-Facilitated Aggregation of Thermo-Sensitive Proteins Shields Them from Degradation during Heat Stress
Chaperone-Facilitated Aggregation of Thermo-Sensitive Proteins Shields Them from Degradation during Heat Stress
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DOI：
10.1016/j.celrep.2020.01.077
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发表时间：
2020-02-18
期刊：
影响因子：
8.8
通讯作者：
Hidalgo, Elena
中科院分区：
文献类型：
--
作者：
Cabrera, Margarita;Boronat, Susanna;Hidalgo, Elena
细胞已经开发出蛋白质质量控制策略来管理热应激期间错误折叠底物的积累。使用一个可溶性的报告错误折叠的裂变酵母，Rho 1. C17 R-GFP，我们证明，在温和的热休克，报告崩溃在蛋白质聚集中心（PAC）。它们含有和/或需要几种分子伴侣，如Hsp 104、Hsp 16和Hsp 40/70对Mas 5/Ssa 2。应力颗粒不组装在温和的温度下，因此，不需要PAC的形成，相反，PAC可以作为成核中心的应力颗粒的组装。与一般的看法相反，这些PAC的主要命运不是降解，并且聚集的报告分子可以被分子伴侣分解并恢复天然结构和活性。使用质谱，我们表明，热不稳定的内源性蛋白质形成PAC以及。总之，热休克过程中PAC的形成是一种分子伴侣介导的适应策略。
Cells have developed protein quality-control strategies to manage the accumulation of misfolded substrates during heat stress. Using a soluble reporter of misfolding in fission yeast, Rho1.C17R-GFP, we demonstrate that upon mild heat shock, the reporter collapses in protein aggregate centers (PACs). They contain and/or require several chaperones, such as Hsp104, Hsp16, and the Hsp40/70 couple Mas5/Ssa2. Stress granules do not assemble at mild temperatures and, therefore, are not required for PAC formation; on the contrary, PACs may serve as nucleation centers for the assembly of stress granules. In contrast to the general belief, the dominant fate of these PACs is not degradation, and the aggregated reporter can be disassembled by chaperones and recovers native structure and activity. Using mass spectrometry, we show that thermo-unstable endogenous proteins form PACs as well. In conclusion, formation of PACs during heat shock is a chaperone-mediated adaptation strategy.