Protein aggregates have negative implications in disease. While reductionist experiments have increased our understanding of aggregation processes, the systemic view in biological context is still limited. To extend this understanding, we used mass spectrometry‐based proteomics to characterize aggregation and disaggregation in human cells after non‐lethal heat shock. Aggregation‐prone proteins were enriched in nuclear proteins, high proportion of intrinsically disordered regions, high molecular mass, high isoelectric point, and hydrophilic amino acids. During recovery, most aggregating proteins disaggregated with a rate proportional to the aggregation propensity: larger loss in solubility was counteracted by faster disaggregation. High amount of intrinsically disordered regions were associated with faster disaggregation. However, other characteristics enriched in aggregating proteins did not correlate with the disaggregation rates. In addition, we analyzed changes in protein thermal stability after heat shock. Soluble remnants of aggregated proteins were more thermally stable compared with control condition. Therefore, our results provide a rich resource of heat stress‐related protein solubility data and can foster further studies related to protein aggregation diseases.

中文翻译：

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人类蛋白质组的聚集和分解特征

蛋白质聚集体对疾病有负面影响。虽然还原论实验增加了我们对聚集过程的理解，但生物学背景下的系统观点仍然有限。为了扩展这种理解，我们使用基于质谱的蛋白质组学来表征非致命热休克后人类细胞的聚集和解聚。易于聚集的蛋白质富含核蛋白、高比例的本质无序区域、高分子量、高等电点和亲水性氨基酸。在恢复过程中，大多数聚集蛋白以与聚集倾向成比例的速率解聚：溶解度的较大损失被更快的解聚所抵消。大量本质上无序的区域与更快的分解有关。然而，聚集蛋白富集的其他特征与解聚率不相关。此外，我们还分析了热激后蛋白质热稳定性的变化。与对照条件相比，聚集蛋白的可溶性残余物具有更高的热稳定性。因此，我们的结果提供了丰富的热应激相关蛋白质溶解度数据资源，可以促进与蛋白质聚集疾病相关的进一步研究。