Karyopherins in nuclear pore biogenesis: a role for Kap121p in the assembly of Nup53p into nuclear pore complexes.
Karyopherins in nuclear pore biogenesis: a role for Kap121p in the assembly of Nup53p into nuclear pore complexes.
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DOI：
10.1083/jcb.200203079
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发表时间：
2002-10-28
影响因子：
7.8
通讯作者：
Wozniak, Richard W
中科院分区：
文献类型：
--
作者：
Lusk, C Patrick;Makhnevych, Taras;Marelli, Marcello;Aitchison, John D;Wozniak, Richard W
控制核孔复合体(NPC)组装的机制在很大程度上仍不清楚。在这里，我们已经确定了核粘附素在这一过程中的作用。我们通过识别Nup53p中的核定位信号(NLS)，证明了酵母核粘附素Kap121p在核孔蛋白Nup53p的靶向和组装成NPC中的作用。如果Nup53p的Kap121p结合域被经典的NLS取代，Kap95p-Kap60p复合体也可以执行这种核粘附素介导的功能，这表明核粘附素在鼻咽癌组装中具有更广泛的作用。在鼻咽癌，邻近的核孔蛋白与Nup53p的两个区域结合。一种名为Nup170p的核孔蛋白与Nup53p的一个区域重叠，该区域与Kap121p结合位点重叠，我们表明它们竞争与Nup53p的结合。我们认为，一旦靶向NPC，Kap121p-Nup53p复合体的解离是由Nup53p与Nup170p的相互作用推动的。在NPC，Nup53p存在于两个独立的复合体中，其中一个能够与Kap121p相互作用，另一个与Nup170p结合。我们认为，这两种状态之间的波动驱动Kap121p从Nup53p结合和释放，从而促进Kap121p在NPC中的移动。
The mechanisms that govern the assembly of nuclear pore complexes (NPCs) remain largely unknown. Here, we have established a role for karyopherins in this process. We show that the yeast karyopherin Kap121p functions in the targeting and assembly of the nucleoporin Nup53p into NPCs by recognizing a nuclear localization signal (NLS) in Nup53p. This karyopherin-mediated function can also be performed by the Kap95p–Kap60p complex if the Kap121p-binding domain of Nup53p is replaced by a classical NLS, suggesting a more general role for karyopherins in NPC assembly. At the NPC, neighboring nucleoporins bind to two regions in Nup53p. One nucleoporin, Nup170p, associates with a region of Nup53p that overlaps with the Kap121p binding site and we show that they compete for binding to Nup53p. We propose that once targeted to the NPC, dissociation of the Kap121p–Nup53p complex is driven by the interaction of Nup53p with Nup170p. At the NPC, Nup53p exists in two separate complexes, one of which is capable of interacting with Kap121p and another that is bound to Nup170p. We propose that fluctuations between these two states drive the binding and release of Kap121p from Nup53p, thus facilitating Kap121p's movement through the NPC.