Allosteric Regulation in Gating the Central Channel of the Nuclear Pore Complex
Allosteric Regulation in Gating the Central Channel of the Nuclear Pore Complex
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DOI：
10.1016/j.cell.2015.05.013
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发表时间：
2015-06-04
期刊：
影响因子：
64.5
通讯作者：
Blobel, Guenter
中科院分区：
文献类型：
--
作者：
Koh, Junseock;Blobel, Guenter
核孔复合体（NPC）在进化过程中成为细胞中最大且功能最多样的运输通道。目前关于核孔复合体介导的选择性运输的模型侧重于核孔蛋白的内在无序区域与运输因子结合的特性。相比之下，结构化区域被认为是为无序区域提供静态锚定位点，而不影响运输因子的结合。在此，我们证明了通道核孔蛋白（Nup58）的一个结构化结构域与其相邻的无序结构域之间存在变构偶联，该无序结构域与另一个通道核孔蛋白（Nup54）和一个运输因子（Kapβ1）相互作用。对多重平衡的分析表明，Kapβ1与Nup58无序结构域的多价相互作用稳定了与Nup54相关的相邻结构化结构域，使构象平衡从同聚体转变为异聚体。基于这些以及先前的晶体学结果，建立了一个定量框架来描述中心通道的收缩和扩张与运输因子占据情况的函数关系。
The nuclear pore complex (NPC) arose in evolution as the cell's largest and most versatile transport channel. Current models for selective transport mediated by NPCs are focused on properties of intrinsically disordered regions of nucleoporins that bind transport factors. In contrast, structured regions are considered to provide static anchoring sites for the disordered regions without affecting transport factor binding. Here, we demonstrate allosteric coupling between a structured domain of a channel nucleoporin (Nup58) and its neighboring disordered domain in interaction with another channel nucleoporin (Nup54) and a transport factor (Kap beta 1). Analysis of multiple equilibria showed that multivalent interactions of Kapb1 with the disordered domains of Nup58 stabilize the neighboring structured domain associated with Nup54, shifting conformational equilibria from homo-oligomers to hetero-oligomers. Based on these and previous crystallographic results, a quantitative framework was established to describe constriction and dilation of the central channel as a function of transport factor occupancy.