Cowburn David, Rout Michael
Depts of Biochemistry and Systems & Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
ArXiv. 2023 Apr 6:arXiv:2304.03230v1.
Nuclear pore complexes (NPCs) mediate the exchange of materials between the nucleoplasm and cytoplasm, playing a key role in the separation of nucleic acids and proteins into their required compartments. The static structure of the NPC is relatively well defined by recent cryo EM and other studies. The functional roles of dynamic components in the pore of the NPC, phenylalanyl-glycyl (FG) repeat rich nucleoporins, is less clear because of our limited understanding of highly dynamic protein systems. These proteins form a restrained concentrate which interacts with and concentrates nuclear transport factors (NTRs) to provide facilitated nucleocytoplasmic transport of cargoes. Very rapid exchange among FG repeats and NTRs supports extremely fast facilitated transport, close to the rate of macromolecular diffusion in cytoplasm, while complexes without specific interactions are entropically excluded, though details on several aspects of the transport mechanism and FG repeat behaviors remain to be resolved. However, as discussed here, new technical approaches combined with more advanced modeling methods will likely provide an improved dynamic description of NPC transport, potentially at the atomic level in the near future. Such advances are likely to be of major benefit in comprehending the roles the malfunctioning NPC plays in cancer, aging, viral diseases, and neurodegeneration.
核孔复合体（NPCs）介导核质与细胞质之间的物质交换，在将核酸和蛋白质分隔到各自所需的区室中起着关键作用。NPC的静态结构通过最近的冷冻电镜和其他研究得到了相对较好的界定。由于我们对高度动态的蛋白质系统了解有限，NPC孔中动态成分（富含苯丙氨酰 - 甘氨酰（FG）重复序列的核孔蛋白）的功能作用尚不清楚。这些蛋白质形成一种受限的浓缩物，与核转运因子（NTRs）相互作用并使其浓缩，以促进货物的核质运输。FG重复序列和NTRs之间非常快速的交换支持了极快的易化运输，接近细胞质中大分子扩散的速率，而没有特异性相互作用的复合物则因熵的原因被排除在外，尽管运输机制和FG重复序列行为的几个方面的细节仍有待解决。然而，如本文所讨论的，新技术方法与更先进的建模方法相结合，可能会在不久的将来提供一个改进的NPC运输动态描述，甚至可能达到原子水平。这样的进展可能对理解功能失调的NPC在癌症、衰老、病毒疾病和神经退行性变中所起的作用有很大帮助。
