Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.
Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.
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DOI：
10.1016/j.cell.2015.08.041
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发表时间：
2015-09-10
期刊：
影响因子：
64.5
通讯作者：
Drummond DA
中科院分区：
文献类型：
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作者：
Wallace EW;Kear-Scott JL;Pilipenko EV;Schwartz MH;Laskowski PR;Rojek AE;Katanski CD;Riback JA;Dion MF;Franks AM;Airoldi EM;Pan T;Budnik BA;Drummond DA
热引起蛋白质错误折叠和聚集，并且在真核细胞中触发蛋白质和RNA聚集成应激颗粒。我们已经进行了广泛的蛋白质组学研究，以量化热引发的聚集和随后的解聚在芽殖酵母，确定超过170个内源性蛋白质聚集在几分钟内的热休克在多个亚细胞区室。我们证明，这些聚集的蛋白质没有错误折叠，注定要降解。稳定的同位素标记表明，即使严重聚集的内源性蛋白质分解，而不降解从休克恢复过程中，与观察到的外源性热不稳定蛋白质的快速降解形成对比。虽然聚集可能使许多细胞蛋白失活，但在异源三聚体氨酰-tRNA合成酶复合物的情况下，聚集的蛋白保持活性，保真度不变。我们建议，大多数热诱导的成熟蛋白质的聚集反映了一个适应性的操作，自动调节过程的功能显着的聚集体组装和拆卸，帮助细胞适应热应激。
Heat causes protein misfolding and aggregation, and in eukaryotic cells triggers aggregation of proteins and RNA into stress granules. We have carried out extensive proteomic studies to quantify heat-triggered aggregation and subsequent disaggregation in budding yeast, identifying more than 170 endogenous proteins aggregating within minutes of heat shock in multiple subcellular compartments. We demonstrate that these aggregated proteins are not misfolded and destined for degradation. Stable-isotope labeling reveals that even severely aggregated endogenous proteins are disaggregated without degradation during recovery from shock, contrasting with the rapid degradation observed for exogenous thermolabile proteins. Although aggregation likely inactivates many cellular proteins, in the case of a heterotrimeric aminoacyl-tRNA synthetase complex, the aggregated proteins remain active with unaltered fidelity. We propose that most heat-induced aggregation of mature proteins reflects the operation of an adaptive, autoregulatory process of functionally significant aggregate assembly and disassembly that aids cellular adaptation to thermal stress.