Stuwe Tobias, Bley Christopher J, Thierbach Karsten, Petrovic Stefan, Schilbach Sandra, Mayo Daniel J, Perriches Thibaud, Rundlet Emily J, Jeon Young E, Collins Leslie N, Huber Ferdinand M, Lin Daniel H, Paduch Marcin, Koide Akiko, Lu Vincent, Fischer Jessica, Hurt Ed, Koide Shohei, Kossiakoff Anthony A, Hoelz André
California Institute of Technology, Division of Chemistry and Chemical Engineering, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Science. 2015 Oct 2;350(6256):56-64. doi: 10.1126/science.aac9176. Epub 2015 Aug 27.
The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional nucleocytoplasmic transport. We present the reconstitution and interdisciplinary analyses of the ~425-kilodalton inner ring complex (IRC), which forms the central transport channel and diffusion barrier of the NPC, revealing its interaction network and equimolar stoichiometry. The Nsp1•Nup49•Nup57 channel nucleoporin heterotrimer (CNT) attaches to the IRC solely through the adaptor nucleoporin Nic96. The CNT•Nic96 structure reveals that Nic96 functions as an assembly sensor that recognizes the three-dimensional architecture of the CNT, thereby mediating the incorporation of a defined CNT state into the NPC. We propose that the IRC adopts a relatively rigid scaffold that recruits the CNT to primarily form the diffusion barrier of the NPC, rather than enabling channel dilation.
核孔复合体（NPC）是核质双向运输的唯一通道。我们展示了约425千道尔顿内环复合体（IRC）的重组和跨学科分析，该复合体构成了NPC的中央运输通道和扩散屏障，揭示了其相互作用网络和等摩尔化学计量比。Nsp1•Nup49•Nup57通道核孔蛋白异源三聚体（CNT）仅通过衔接核孔蛋白Nic96附着于IRC。CNT•Nic96结构表明，Nic96作为一种组装传感器，识别CNT的三维结构，从而介导特定CNT状态纳入NPC。我们提出，IRC采用相对刚性的支架招募CNT，主要形成NPC的扩散屏障，而非实现通道扩张。
