The molecular mechanism of nuclear transport revealed by atomic-scale measurements
The molecular mechanism of nuclear transport revealed by atomic-scale measurements
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DOI：
10.7554/elife.10027
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发表时间：
2015-09-15
期刊：
影响因子：
7.7
通讯作者：
Cowburn, David
中科院分区：
文献类型：
--
作者：
Hough, Loren E.;Dutta, Kaushik;Cowburn, David
核孔复合物（npc）形成一个选择性过滤器，允许转运因子（tf）及其货物快速通过核包膜，同时阻止其他大分子的通过。含有富苯丙烯酰甘酰基（FG）重复序列的内在无序蛋白（IDPs）排列在孔中并与tf相互作用。然而，由于缺乏关于fg行为及其与tf相互作用的原子尺度信息，输运既快又特异的原因仍未确定。我们使用核磁共振波谱来解决这些问题。我们发现FG重复序列是高度动态的IDPs，由细胞环境稳定。支持tf的快速传输，因为FG基序的快速运动允许它们通过瞬态相互作用非常快速地交换tf的开关。因为tf独特地携带了多个FG重复片段，所以只有它们才能形成许多频繁的相互作用，从而使FG重复片段之间的特定通道能够穿过NPC。
Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC.