Both natively folded and intrinsically disordered proteins (IDPs) destined for the nucleus need to transport through the nuclear pore complexes (NPCs) in eukaryotic cells. NPCs allow for passive diffusion of small folded proteins while barricading large ones, unless they are facilitated by nuclear transport receptors. However, whether nucleocytoplasmic transport of IDPs would follow these rules remains unknown. By using a high-speed super-resolution fluorescence microscopy, we have measured transport kinetics and 3D spatial locations of transport routes through native NPCs for various IDPs. Our data revealed that the rules executed for folded proteins are not well followed by the IDPs. Instead, both large and small IDPs can passively diffuse through the NPCs. Furthermore, their diffusion efficiencies and routes are differentiated by their content ratio of charged (Ch) and hydrophobic (Hy) amino acids. A Ch/Hy-ratio mechanism was finally suggested for nucleocytoplasmic transport of IDPs.

中文翻译：

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内在无序蛋白的核质运输通过高速超高分辨率显微镜研究。

天然的折叠蛋白和固有的无序蛋白（IDP）都必须通过核内的核孔复合体（NPC）转运至细胞核。NPC允许小折叠的蛋白质被动扩散，而阻止大的折叠蛋白质，除非它们由核转运受体促进。但是，IDP的核质运输是否会遵循这些规则仍是未知的。通过使用高速超高分辨率荧光显微镜，我们已经测量了各种IDP通过天然NPC的运输动力学和运输路线的3D空间位置。我们的数据表明，针对折叠蛋白执行的规则并没有很好地遵循IDP。相反，大型和小型IDP都可以通过NPC被动扩散。此外，它们的扩散效率和途径通过带电荷的（Ch）和疏水的（Hy）氨基酸的含量比来区分。最后提出了Ch / Hy比机制用于IDP的核质运输。