Charge of karyopherins and nuclear FG-Nups are key ingredients of nucleocytoplasmic transport.

IF 3.2 3区 生物学 Q2 BIOPHYSICS Biophysical journal Pub Date : 2024-11-25 DOI:10.1016/j.bpj.2024.11.3313
Ankur Mishra, Erik Van der Giessen, Patrick R Onck
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Abstract

The nuclear pore complex (NPC) is responsible for the selective transport of biomolecules in and out of the nucleus. This selective feature is achieved through intrinsically disordered proteins, FG-nups, that are anchored to the inner wall of the NPC. Cargo smaller than approximately 5 nm can rapidly diffuse through the NPC whereas larger cargo is increasingly slowed down. Larger cargos bound to chaperone proteins (from the karyopherin or Kap family) can still be transported due to non-specific interactions with the FG-Nups. Although various mechanisms for the transport of Kaps have been proposed, a consensus has still to be reached. Here we conducted a coarse-grained molecular dynamics study to shed light on Kap translocation through NPCs. We investigated the effect of Kap surface charge and hydrophobicity on the transport rate. We found that the negative charge of the Kaps is essential for transport whereas Kap hydrophobicity of the transport particle aids in the translocation. Interestingly, our results indicate that the positive net charge of the nuclear Nups (especially Nup1) is instrumental for the transport of Kaps, revealing a (previously proposed) gradient of increasing binding affinity of the Kaps with FG-Nups from the cytoplasm to the nucleus.

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核糖体蛋白和核FG-Nups的电荷是核细胞质运输的关键因素。
核孔复合体(NPC)负责将生物大分子有选择地运入和运出细胞核。这种选择性功能是通过锚定在核孔复合体内壁上的固有无序蛋白(FG-nups)实现的。小于约 5 纳米的货物可以快速扩散通过 NPC,而较大的货物则会越来越慢。由于与 FG-Nups 的非特异性相互作用,与伴侣蛋白(来自 karyopherin 或 Kap 家族)结合的较大货物仍可被运输。尽管人们提出了各种 Kaps 运输机制,但仍未达成共识。在此,我们进行了一项粗粒度分子动力学研究,以揭示 Kap 通过 NPC 的转运。我们研究了 Kap 表面电荷和疏水性对转运速率的影响。我们发现,Kap的负电荷对转运至关重要,而转运粒子的Kap疏水性则有助于转运。有趣的是,我们的研究结果表明,核Nups(尤其是Nup1)的正净电荷有助于Kaps的运输,揭示了(以前提出的)Kaps与FG-Nups的结合亲和力从细胞质到细胞核的梯度增加。
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来源期刊
Biophysical journal
Biophysical journal 生物-生物物理
CiteScore
6.10
自引率
5.90%
发文量
3090
审稿时长
2 months
期刊介绍: BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.
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