Department of Bioengineering, University of California, Berkeley, California, USA.
Int Rev Cell Mol Biol. 2011;287:233-86. doi: 10.1016/B978-0-12-386043-9.00006-2.
Nuclear pore complexes (NPCs) are the gateways connecting the nucleoplasm and cytoplasm. This structures are composed of over 30 different proteins and 60-125 MDa of mass depending on type of species. NPCs are bilateral pathways that selectively control the passage of macromolecules into and out of the nucleus. Molecules smaller than 40 kDa diffuse through the NPC passively while larger molecules require facilitated transport provided by their attachment to karyopherins. Kinetic studies have shown that approximately 1000 translocations occur per second per NPC. Maintaining its high selectivity while allowing for rapid translocation makes the NPC an efficient chemical nanomachine. In this review, we approach the NPC function via a structural viewpoint. Putting together different pieces of this puzzle, this chapter confers an overall insight into what molecular processes are engaged in import/export of active cargos across the NPC and how different transporters regulate nucleocytoplasmic transport. In the end, the correlation of several diseases and disorders with the NPC structural defects and dysfunctions is discussed.
核孔复合体(NPC)是连接核质和细胞质的通道。这些结构由超过 30 种不同的蛋白质组成,质量为 60-125MDa,具体取决于物种类型。NPC 是双侧途径,选择性地控制大分子进入和离开细胞核的通道。小于 40kDa 的分子通过 NPC 被动扩散,而较大的分子则需要通过与核转运蛋白的结合来提供易化运输。动力学研究表明,每个 NPC 每秒大约有 1000 次转位发生。在保持高选择性的同时允许快速转位,使得 NPC 成为一种高效的化学纳米机器。在这篇综述中,我们从结构的角度来探讨 NPC 的功能。通过将这个难题的不同部分放在一起,本章全面了解了分子过程是如何参与 NPC 上主动货物的进出口的,以及不同的转运蛋白如何调节核质转运。最后,讨论了几种疾病和障碍与 NPC 结构缺陷和功能障碍的相关性。