A self-inhibitory interaction within Nup155 and membrane binding are required for nuclear pore complex formation
A self-inhibitory interaction within Nup155 and membrane binding are required for nuclear pore complex formation
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DOI：
10.1242/jcs.208538
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Antonin, Wolfram
中科院分区：
文献类型：
--
作者：
De Magistris, Paola;Tatarek-Nossol, Marianna;Antonin, Wolfram
核孔复合体（nuclear pore complex，NPC）是穿过核膜的通道。它们如何形成含有三环的结构并整合到核膜中仍然是协调组装大复合物的具有挑战性的范例。在脊椎动物中，NPC的细胞质环和核质环主要由Nup 107-Nup 160复合物的多个拷贝形成，而中央或内环由Nup 53、Nup 93、Nup 155和两个旁系同源物Nup 188和Nup 205组成。内圈装配只是部分理解。使用体外核组装反应，我们表明，直接孔膜结合的Nup 155是至关重要的NPC形成。用其N-末端β-螺旋桨取代全长Nup 155允许将外环组件组装到也包含Nup 53的NPC骨架上。然而，进一步的组装，特别是Nup 93和Nup 62复合物的募集被阻断。Nup 155的N-和C-末端结构域之间的自身相互作用具有阻止Nup 155的N-末端和Nup 53的C-末端区域之间相互作用的自抑制功能。Nup 93可以通过与Nup 53结合来克服这种阻断，从而促进内环和NPC的形成。
Nuclear pore complexes (NPCs) are gateways through the nuclear envelope. How they form into a structure containing three rings and integrate into the nuclear envelope remains a challenging paradigm for coordinated assembly of macro-complexes. In vertebrates, the cytoplasmic and nucleoplasmic rings of NPCs are mostly formed by multiple copies of the Nup107-Nup160 complex, whereas the central, or inner ring is composed of Nup53, Nup93, Nup155 and the two paralogues Nup188 and Nup205. Inner ring assembly is only partially understood. Using in vitro nuclear assembly reactions, we show that direct pore membrane binding of Nup155 is crucial for NPC formation. Replacing full-length Nup155 with its N-terminal beta-propeller allows assembly of the outer ring components to the NPC backbone that also contains Nup53. However, further assembly, especially recruitment of the Nup93 and Nup62 complexes, is blocked. Self-interaction between the N- and C-terminal domains of Nup155 has an auto-inhibitory function that prevents interaction between the N-terminus of Nup155 and the C-terminal region of Nup53. Nup93 can overcome this block by binding to Nup53, thereby promoting formation of the inner ring and the NPC.