Meng Fanchi, Na Insung, Kurgan Lukasz, Uversky Vladimir N
Department of Electrical and Computer Engineering, University of Alberta, Edmonton, AB T6G 2V4, Canada.
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Int J Mol Sci. 2015 Dec 25;17(1):24. doi: 10.3390/ijms17010024.
The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions.
细胞核包含许多无膜细胞器或核内区室。这些区室是动态结构，代表液滴相，其密度仅略高于核内主体流体。它们具有不同的功能，形态多样，通常由RNA（或在某些情况下由DNA）和蛋白质组成。我们分析了3005种定位于特定核内细胞器（如核仁、染色质、卡哈尔体、核斑点、早幼粒细胞白血病（PML）核体、核纤层、核孔和核周区室）的小鼠蛋白质，并将它们与来自小鼠蛋白质组的约29863种非核蛋白质进行了比较。我们的分析表明，除了核孔和核纤层外，大多数核内区室中内在无序性都很丰富。这些区室中缺乏无序结构域的蛋白质较少，而具有多个无序结构域的蛋白质较多。在多个核内区室中发现的兼职蛋白质更有可能具有多个无序结构域。与非核蛋白质相比，核内区室中的蛋白质-蛋白质相互作用网络更密集，包含更多的枢纽蛋白。与非核枢纽蛋白和非核蛋白质相比，核内区室中的枢纽蛋白（核孔除外）无序性更丰富。因此，我们的工作为细胞核中内在无序性的功能重要性这一观点提供了支持，并表明许多与小鼠细胞核内亚核细胞器相关的蛋白质无序性丰富。小鼠核蛋白中这种高水平的无序性决定了它们作为非常混杂的结合剂的能力，既拥有大量潜在的基于无序性的相互作用位点，又具有单个这样的位点参与大量相互作用的能力。
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