Structural and functional studies of Nup107/Nup133 interaction and its implications for the architecture of the nuclear pore complex
Structural and functional studies of Nup107/Nup133 interaction and its implications for the architecture of the nuclear pore complex
复制标题
DOI：
10.1016/j.molcel.2008.04.022
复制
发表时间：
2008-06-20
期刊：
影响因子：
16
通讯作者：
Schwartz, Thomas U.
中科院分区：
文献类型：
--
作者：
Boehmer, Thomas;Jeudy, Sandra;Schwartz, Thomas U.
核孔复合物（Nuclear pore complex，NPC）是一组分子量为40-60 MDa的蛋白质，分布于真核细胞的核膜中。NPC专门介导细胞质和细胞核之间的所有运输。构建NPC的核孔蛋白排列在具有八重旋转对称性的模块样亚复合物的稳定核心中。为了深入了解NPC的复杂组装，我们已经解决了两个核孔蛋白Nup 107和Nup 133之间的蛋白质复合物的晶体结构。这两种蛋白质形成细长的结构，通过紧凑的界面以尾对尾的方式紧密相互作用。使用结构导向突变体的其他实验表明，Nup 107是Nup 133与NPC的关键锚，将Nup 133定位在NPC的外围。Nup 107和Nup 133之间的显著拓扑差异表明NPC支架的α-螺旋核孔蛋白结构域属于不同的类别，并且实现了很大程度上非冗余的功能。
Nuclear pore complexes (NPCs) are 40-60 MDa protein assemblies embedded in the nuclear envelope of eukaryotic cells. NPCs exclusively mediate all transport between cytoplasm and nucleus. The nucleoporins that build the NPC are arranged in a stable core of module-like subcomplexes with eight-fold rotational symmetry. To gain insight into the intricate assembly of the NPC, we have solved the crystal structure of a protein complex between two nucleoporins, human Nup107 and Nup133. Both proteins form elongated structures that interact tightly via a compact interface in tail-to-tail fashion. Additional experiments using structure-guided mutants show that Nup107 is the critical anchor for Nup133 to the NPC, positioning Nup133 at the periphery of the NPC. The significant topological differences between Nup107 and Nupl 33 suggest that alpha-helical nucleoporin domains of the NPC scaffold fall in different classes and fulfill largely nonredundant functions.