Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Cell. 2018 May 31;173(6):1495-1507.e18. doi: 10.1016/j.cell.2018.03.053. Epub 2018 Apr 26.
Quantitative mass spectrometry has established proteome-wide regulation of protein abundance and post-translational modifications in various biological processes. Here, we used quantitative mass spectrometry to systematically analyze the thermal stability and solubility of proteins on a proteome-wide scale during the eukaryotic cell cycle. We demonstrate pervasive variation of these biophysical parameters with most changes occurring in mitosis and G1. Various cellular pathways and components vary in thermal stability, such as cell-cycle factors, polymerases, and chromatin remodelers. We demonstrate that protein thermal stability serves as a proxy for enzyme activity, DNA binding, and complex formation in situ. Strikingly, a large cohort of intrinsically disordered and mitotically phosphorylated proteins is stabilized and solubilized in mitosis, suggesting a fundamental remodeling of the biophysical environment of the mitotic cell. Our data represent a rich resource for cell, structural, and systems biologists interested in proteome regulation during biological transitions.
定量质谱已经在各种生物学过程中建立了蛋白质丰度和翻译后修饰的蛋白质组范围的调控。在这里，我们使用定量质谱在真核细胞周期中系统地分析了蛋白质的热稳定性和溶解度的蛋白质组范围。我们证明了这些生物物理参数的普遍变化，大多数变化发生在有丝分裂和 G1 期。各种细胞途径和成分的热稳定性不同，如细胞周期因子、聚合酶和染色质重塑因子。我们证明，蛋白质热稳定性可以作为酶活性、DNA 结合和原位复合物形成的替代物。引人注目的是，大量的内在无序和有丝分裂磷酸化蛋白质在有丝分裂中稳定和溶解，这表明有丝分裂细胞的生物物理环境发生了根本性的重塑。我们的数据为对生物转变过程中蛋白质组调控感兴趣的细胞、结构和系统生物学家提供了丰富的资源。
