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APS -Annual Meeting of the APS Four Corners Section- Event - Mechanisms of selective transport through nuclear pore complex mimics

机译:APS-APS四角区年会-活动-通过核孔复合物模拟物进行选择性转运的机制

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Few cellular processes require such intricate active control as transport through the nuclear envelope. The nuclear pore complex (NPC) facilitates all transport, preventing most macromolecules from crossing the envelope while allowing the passage of transport factors (TFs) and their cargo. While the basic biochemical interactions of transport are well-understood, the detailed mechanism remains a topic of significant debate. We create tunable mimics of the NPC using PEG hydrogels filled with FG nucleoporins (FG nups), the intrinsically disordered proteins that line the NPC channel in vivo. We also model transport using reaction-diffusion equations. The results suggest that (1) the flexible nature of the disordered FG nups and (2) the transient, multivalent nature of FG nup -- TF interactions are together sufficient for selectivity. Our model makes selectivity predictions that will be directly testable in our experimental setup. We aim to use the model to tune the mimic's parameters to maximize selectivity.
机译:很少有细胞过程需要如此复杂的主动控制,例如通过核被膜的转运。核孔复合物(NPC)促进了所有运输,从而防止大多数大分子穿过包膜,同时允许运输因子(TF)及其货物通过。虽然运输的基本生化相互作用已被很好地理解,但详细的机制仍然是一个有争议的话题。我们使用充满FG核孔蛋白(FG nups)的PEG水凝胶创建NPC的可调谐模拟物,FG核孔蛋白是在体内排列NPC通道的内在无序蛋白。我们还使用反应扩散方程对运输进行建模。结果表明(1)无序的FG nups的柔性性质和(2)FG nup-TF相互作用的瞬时多价性质共同足以实现选择性。我们的模型做出的选择性预测可以在我们的实验设置中直接进行测试。我们旨在使用该模型来调整模拟参数,以最大程度地提高选择性。

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