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Global Motions of the Nuclear Pore Complex: Insights from Elastic Network Models

机译:核孔复合体的全球运动:来自弹性网络模型的见解

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摘要

The nuclear pore complex (NPC) is the gate to the nucleus. Recent determination of the configuration of proteins in the yeast NPC at ∼5 nm resolution permits us to study the NPC global dynamics using coarse-grained structural models. We investigate these large-scale motions by using an extended elastic network model (ENM) formalism applied to several coarse-grained representations of the NPC. Two types of collective motions (global modes) are predicted by the ENMs to be intrinsically favored by the NPC architecture: global bending and extension/contraction from circular to elliptical shapes. These motions are shown to be robust against tested variations in the representation of the NPC, and are largely captured by a simple model of a toroid with axially varying mass density. We demonstrate that spoke multiplicity significantly affects the accessible number of symmetric low-energy modes of motion; the NPC-like toroidal structures composed of 8 spokes have access to highly cooperative symmetric motions that are inaccessible to toroids composed of 7 or 9 spokes. The analysis reveals modes of motion that may facilitate macromolecular transport through the NPC, consistent with previous experimental observations.
机译:核孔复合体(NPC)是通往核的门。最近在〜5 nm分辨率下确定酵母NPC中蛋白质构型的方法,使我们能够使用粗粒结构模型研究NPC的整体动力学。我们通过使用扩展弹性网络模型(ENM)形式主义应用于NPC的几种粗粒度表示形式来研究这些大规模运动。 ENM预测两种类型的集体运动(整体模式)在本质上会受到NPC体系结构的支持:整体弯曲以及从圆形到椭圆形的伸展/收缩。这些运动显示出对NPC表示中经过测试的变化具有鲁棒性,并且很大程度上被具有轴向变化质量密度的环形的简单模型所捕获。我们证明,辐条的多重性显着影响对称的低能量运动模式的可访问数量。由8个辐条组成的类似NPC的环形结构可以访问高度协作的对称运动,而对称运动由7个或9个辐条组成。分析揭示了可能促进大分子通过NPC转运的运动方式,这与以前的实验观察一致。

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