Charge as a selection criterion for translocation through the nuclear pore complex.
Charge as a selection criterion for translocation through the nuclear pore complex.
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DOI：
10.1371/journal.pcbi.1000747
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发表时间：
2010-04-22
影响因子：
4.3
通讯作者：
Ribbeck K
中科院分区：
文献类型：
--
作者：
Colwell LJ;Brenner MP;Ribbeck K
核孔复合物（NPC）是高度选择性的过滤器，控制细胞核和细胞质之间的物质交换。NPC选择性过滤的原理还没有完全被理解。以往的研究发现，能够通过NPC（转运受体）快速转运的细胞蛋白的特征在于高比例的疏水表面区域。我们的分析发现，转运受体及其复合物也是高度负电荷的。此外，构成渗透屏障的NPC组分带正电荷。我们估计，运输受体和NPC之间的静电相互作用的结果在几个K B T的能量增益，这将使运输受体相对于其他细胞蛋白的易位率显着增加。我们认为，负电荷是选择性通过NPC的一个重要标准。所有在细胞质和细胞核之间移动的蛋白质都必须通过核孔复合物，即直径约40 nm的大型水通道。在某些情况下，核被膜上有数千个核孔复合体，而在其他情况下，它们很少。通过核孔的大分子运输受到高度调节;一个复杂的系统，涉及辅助蛋白（运输受体）的结合和解结合，允许调节哪些蛋白质可以通过孔。支配这种选择性过滤的基本原理还没有被完全理解。一些蛋白质通过孔而不与转运受体结合，而另一些蛋白质需要结合多个转运受体以进行有效转运。小孔如何选择哪些蛋白质可以通过，哪些不能？本文进行了一个生物物理分析的性质，蛋白质，可以通过核孔易位。我们发现，能够快速易位的蛋白质是高度负电荷，而不能通过孔的蛋白质是带正电荷的。此外，构成孔道内部的蛋白质本身带净正电荷。这表明转运蛋白和孔之间的静电相互作用是选择性过滤机制的重要组成部分。
Nuclear pore complexes (NPCs) are highly selective filters that control the exchange of material between nucleus and cytoplasm. The principles that govern selective filtering by NPCs are not fully understood. Previous studies find that cellular proteins capable of fast translocation through NPCs (transport receptors) are characterized by a high proportion of hydrophobic surface regions. Our analysis finds that transport receptors and their complexes are also highly negatively charged. Moreover, NPC components that constitute the permeability barrier are positively charged. We estimate that electrostatic interactions between a transport receptor and the NPC result in an energy gain of several k B T, which would enable significantly increased translocation rates of transport receptors relative to other cellular proteins. We suggest that negative charge is an essential criterion for selective passage through the NPC. All proteins that move between the cytoplasm and the nucleus must pass through nuclear pore complexes, large aqueous channels around 40nm in diameter. In some cases the nuclear envelope is perforated with several thousand nuclear pore complexes, while in other cases they are few and far between. Macromolecular transport through nuclear pores is highly regulated; an elaborate system, involving the binding and unbinding of accessory proteins (transport receptors), allows regulation of which proteins can pass through the pores. The basic principles that govern this selective filtering are not fully understood. Some proteins pass through the pore without binding to transport receptors, while others require the binding of multiple transport receptors for efficient translocation. How does the pore select which proteins can pass through, and which cannot? This paper carries out a biophysical analysis of the properties of proteins that can translocate through the nuclear pore. We find that proteins capable of fast translocation are highly negatively charged, whereas proteins that cannot pass through the pore are positively charged. Moreover, proteins that constitute the interior of the pore channel itself are net positively charged. This suggests that electrostatic interactions between translocating proteins and the pore are an essential part of the selective filtering mechanism.
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影响因子：
9.2
作者：
Fagotto, F;Glück, U;Gumbiner, BM
通讯作者：
Gumbiner, BM
影响因子：
56.9
作者：
Frey, Steffen;Richter, Ralf P.;Goerlich, Dirk
通讯作者：
Goerlich, Dirk
影响因子：
64.5
作者：
Bayliss, R;Littlewood, T;Stewart, M
通讯作者：
Stewart, M
DOI：
10.1083/jcb.109.3.971
发表时间：
1989-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Akey CW;Goldfarb DS
通讯作者：
Goldfarb DS
影响因子：
9.2
作者：
Englmeier, L;Olivo, JC;Mattaj, IW
通讯作者：
Mattaj, IW