Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003 Barcelona, Spain.
Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003 Barcelona, Spain.
Cell Rep. 2020 Feb 18;30(7):2430-2443.e4. doi: 10.1016/j.celrep.2020.01.077.
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.
细胞已经开发出蛋白质质量控制策略来管理在热应激期间错误折叠底物的积累。使用裂殖酵母中错误折叠的可溶性报告蛋白 Rho1.C17R-GFP，我们证明在轻度热激时，报告蛋白在蛋白质聚集中心（PAC）中发生了聚集。它们包含和/或需要几种伴侣蛋白，如 Hsp104、Hsp16 和 Hsp40/70 伴侣 Mas5/Ssa2。应激颗粒不会在温和温度下组装，因此不需要形成 PAC；相反，PAC 可能作为应激颗粒组装的成核中心。与普遍的看法相反，这些 PAC 的主要命运不是降解，并且聚集的报告蛋白可以被伴侣蛋白解聚，并恢复其天然结构和活性。使用质谱法，我们还表明不稳定的内源性蛋白质也形成 PAC。总之，热激期间 PAC 的形成是一种伴侣介导的适应策略。
