Nuclear pore complexes (NPCs) are embedded in the nuclear envelope and built from ∼30 different nucleoporins (Nups) in multiple copies, few are integral membrane proteins. One of these transmembrane nucleoporins, Ndc1, is thought to function in NPC assembly at the fused inner and outer nuclear membranes. Here, we show a direct interaction of Ndc1’s transmembrane domain with Nup120 and Nup133, members of the pore membrane coating Y-complex. We identify an amphipathic helix in Ndc1’s C-terminal domain binding highly curved liposomes. Upon overexpression, this amphipathic motif is toxic and dramatically alters the intracellular membrane organization in yeast. Ndc1’s amphipathic motif functionally interacts with related motifs in the C-terminus of the nucleoporins Nup53 and Nup59, important for pore membrane binding and interconnecting NPC modules. The essential function of Ndc1 can be suppressed by deleting the amphipathic helix from Nup53. Our data indicate that nuclear membrane and presumably NPC biogenesis depends on a balanced ratio between amphipathic motifs in diverse nucleoporins.

中文翻译：

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Ndc1 中的不同结构域介导其与 Nup84 复合物和核膜的相互作用

核孔复合物 (NPC) 嵌入核膜中，由约 30 种不同的核孔蛋白 (Nups) 形成多个拷贝，很少是完整的膜蛋白。其中一种跨膜核孔蛋白 Ndc1，被认为在融合的内核膜和外核膜处的 NPC 组装中发挥作用。在这里，我们展示了 Ndc1 跨膜结构域与 Nup120 和 Nup133（孔膜涂层 Y 复合物的成员）的直接相互作用。我们在 Ndc1 的 C 端结构域中发现了一个两亲性螺旋，可结合高度弯曲的脂质体。过度表达后，这种两亲基序具有毒性，会显着改变酵母的细胞内膜组织。Ndc1 的两亲基序在功能上与核孔蛋白 Nup53 和 Nup59 C 端的相关基序相互作用，这对于孔膜结合和互连 NPC 模块很重要。通过从 Nup53 中删除两亲螺旋可以抑制 Ndc1 的基本功能。我们的数据表明，核膜和可能的 NPC 生物发生取决于不同核孔蛋白中两亲基序之间的平衡比例。