Department of Biology, Temple University, Philadelphia, Pennsylvania.
Protein Sci. 2020 Jun;29(6):1459-1472. doi: 10.1002/pro.3845. Epub 2020 Mar 3.
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.
天然折叠和无规卷曲蛋白质（IDPs）都需要穿过真核细胞的核孔复合体（NPC）才能进入细胞核。NPC 允许小分子折叠蛋白通过，但会阻止大分子蛋白通过，除非它们被核转运受体协助。然而，IDPs 的核质转运是否遵循这些规则尚不清楚。通过使用高速超分辨率荧光显微镜，我们已经测量了各种 IDPs 通过天然 NPC 的运输动力学和 3D 空间位置。我们的数据表明，执行折叠蛋白的规则并不完全适用于 IDPs。相反，大的和小的 IDPs 都可以通过 NPC 被动扩散。此外，它们的扩散效率和途径可以通过它们所带电荷（Ch）和疏水性（Hy）氨基酸的含量比例来区分。最后提出了一个 Ch/Hy-ratio 机制，用于 IDPs 的核质转运。
