Surface Properties Determining Passage Rates of Proteins through Nuclear Pores
Surface Properties Determining Passage Rates of Proteins through Nuclear Pores
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DOI：
10.1016/j.cell.2018.05.045
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发表时间：
2018-06-28
期刊：
影响因子：
64.5
通讯作者：
Goerlich, Dirk
中科院分区：
文献类型：
--
作者：
Frey, Steffen;Rees, Renate;Goerlich, Dirk
核孔复合物（NPC）通过FG结构域控制的屏障进行核质转运。我们现在探讨如何表面特征的移动的物种决定其NPC通过率。负电荷和赖氨酸阻碍通道。疏水残基，某些极性残基（半胱氨酸，组氨酸），令人惊讶的是，带电的精氨酸具有显着的易位促进作用。有利的阳离子p之间的相互作用的cation-p的cation-p和FG-苯丙氨酸可以解释这一明显的矛盾。应用这些原理重新设计GFP的表面，产生了显示出宽范围的转运速率的变体，从比野生型慢35倍到快500倍，后者甚至超过了天然存在的核转运受体（NTR）。快速且特别是FG特异性的GFP NTR变体的结构说明了NTR如何能够暴露多个区域以结合疏水性FG基序，同时避免非特异性聚集。最后，我们的文件，即使是NTR介导的运输，表面性质的“被动携带”的货物可以显着影响易位率。
Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport through an FG domain-controlled barrier. We now explore how surface-features of a mobile species determine its NPC passage rate. Negative charges and lysines impede passage. Hydrophobic residues, certain polar residues (Cys, His), and, surprisingly, charged arginines have striking translocation-promoting effects. Favorable cation-p interactions between arginines and FG-phenylalanines may explain this apparent paradox. Application of these principles to redesign the surface of GFP resulted in variants that show a wide span of transit rates, ranging from 35-fold slower than wild-type to similar to 500 times faster, with the latter outpacing even naturally occurring nuclear transport receptors (NTRs). The structure of a fast and particularly FG-specific GFP NTR variant illustrates how NTRs can expose multiple regions for binding hydrophobic FG motifs while evading nonspecific aggregation. Finally, we document that even for NTR-mediated transport, the surface-properties of the "passively carried'' cargo can strikingly affect the translocation rate.