Andersen Kasper R, Onischenko Evgeny, Tang Jeffrey H, Kumar Pravin, Chen James Z, Ulrich Alexander, Liphardt Jan T, Weis Karsten, Schwartz Thomas U
Department of Biology , Massachusetts Institute of Technology , Cambridge , United States.
Elife. 2013 Jun 11;2:e00745. doi: 10.7554/eLife.00745.
Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs) embedded in the nuclear envelope. About 30 different proteins (nucleoporins, nups) arrange around a central eightfold rotational axis to build the modular NPC. Nup188 and Nup192 are related and evolutionary conserved, large nucleoporins that are part of the NPC scaffold. Here we determine the structure of Nup188. The protein folds into an extended stack of helices where an N-terminal 130 kDa segment forms an intricate closed ring, while the C-terminal region is a more regular, superhelical structure. Overall, the structure has distant similarity with flexible S-shaped nuclear transport receptors (NTRs). Intriguingly, like NTRs, both Nup188 and Nup192 specifically bind FG-repeats and are able to translocate through NPCs by facilitated diffusion. This blurs the existing dogma of a clear distinction between stationary nups and soluble NTRs and suggests an evolutionary relationship between the NPC and the soluble nuclear transport machinery. DOI:http://dx.doi.org/10.7554/eLife.00745.001.
核质运输由嵌入核膜的核孔复合体（NPC）介导。大约30种不同的蛋白质（核孔蛋白，nups）围绕着一个中心八重旋转轴排列，构建了模块化的NPC。Nup188和Nup192相关且在进化上保守，是NPC支架的一部分的大型核孔蛋白。在这里，我们确定了Nup188的结构。该蛋白质折叠成一个延伸的螺旋堆叠，其中N端130 kDa片段形成一个复杂的闭环，而C端区域是一个更规则的超螺旋结构。总体而言，该结构与灵活的S形核运输受体（NTR）有远距离相似性。有趣的是，与NTR一样，Nup188和Nup192都特异性结合FG重复序列，并能够通过易化扩散穿过NPC。这模糊了现有的关于固定核孔蛋白和可溶性NTR之间明确区分的教条，并暗示了NPC与可溶性核运输机制之间的进化关系。DOI:http://dx.doi.org/10.7554/eLife.00745.001
