Deciphering the "Fuzzy" Interaction of FG Nucleoporins and Transport Factors Using Small-Angle Neutron Scattering.

Deciphering the "Fuzzy" Interaction of FG Nucleoporins and Transport Factors Using Small-Angle Neutron Scattering.
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DOI:
10.1016/j.str.2018.01.010
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发表时间:
2018-03-06
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Cowburn D
Cowburn D
中科院分区:
其他
文献类型:
--
作者:
Sparks S;Temel DB;Rout MP;Cowburn D

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富含苯丙氨酸-甘氨酸的核孔蛋白(FG-NUP)本质上是无序的,这是一种选择性机制,使运输因子(TF)能够通过核孔复合体(NPC)快速转移。鼻咽癌运输的相互矛盾的模型认为,FG核蛋白在与TFS相互作用时经历不同的构象转变。为了选择性地表征TFS诱导的FG NUP的构象变化,我们进行了对比度匹配的小角中子散射(SANS)。来自SANS的构象系综数据表明,FG NUPS总尺寸的增加与Tf相互作用有关。此外,FG基序在相互作用状态下的组织结构与先前的实验分析一致,这些实验分析定义了FG基序在与TF相互作用时经历构象限制。这些结果为高度动态的相互作用提供了结构性的见解,并说明了功能障碍如何带来快速和选择性的FG Nup-Tf相互作用。斯帕克斯等人。利用小角中子散射实验描述了无序的FG核与来自核孔复合体的传输因子之间的模糊相互作用,从而阐明了传输因子在FG Nup链中引起的微妙构象变化。这项研究有助于定义中等长度尺度下的“模糊性”。
The largely intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG Nups) underline a selectivity mechanism, which enables the rapid translocation of transport factors (TFs) through the nuclear pore complexes (NPCs). Conflicting models of NPC transport have assumed that FG Nups undergo different conformational transitions upon interacting with TFs. To selectively characterize conformational changes in FG Nups induced by TFs we performed small-angle neutron scattering (SANS) with contrast matching. Conformational ensembles derived SANS data indicate an increase in the overall size of FG Nups is associated with TF interaction. Moreover, the organization of the FG motif in the interacting state is consistent with prior experimental analyses defining that FG motifs undergo conformational restriction upon interacting with TFs. These results provide structural insights into a highly dynamic interaction and illustrate how functional disorder imparts rapid and selective FG Nup – TF interactions. Sparks et al. use small angle neutron scattering experiments to describe the fuzzy interactions between disordered FG Nups and transport factors (TFs) from the nuclear pore complex, thus elucidating the subtle conformational changes that TFs induce within FG Nup chains. The study helps to define ‘fuzziness’ at intermediate length scales.
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