The cellular environment shapes the nuclear pore complex architecture.
The cellular environment shapes the nuclear pore complex architecture.
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DOI：
10.1038/s41586-021-03985-3
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发表时间：
2021-10
期刊：
影响因子：
64.8
通讯作者：
Schwartz TU
中科院分区：
文献类型：
--
作者：
Schuller AP;Wojtynek M;Mankus D;Tatli M;Kronenberg-Tenga R;Regmi SG;Dip PV;Lytton-Jean AKR;Brignole EJ;Dasso M;Weis K;Medalia O;Schwartz TU
核孔复合物（NPC）产生用于跨核膜（NE）在细胞核和细胞质之间运输货物的大管道。这些多兆道尔顿结构由大约30种不同的核孔蛋白组成，它们分布在中央运输通道周围的三个主要亚结构（内环、胞质环和核质环）中。在这里，我们使用冷冻电子断层扫描对DLD-1细胞，使用冷冻聚焦离子束铣削制备，以生成在其自然环境中的人NPC的结构模型。我们表明，与以前的人鼻咽癌模型纯化的神经元-在我们的模型中的内环是大幅扩大，中央通道的体积增加了75%，核质和细胞质环重组。此外，NPC膜在内环复合物周围表现出不对称性。使用靶向降解Nup 96，细胞质和核质环的支架核孔蛋白，我们观察到每个环在调节中央通道和维持膜不对称性方面的相互依赖性。我们的研究结果突出了NPC固有的灵活性，并表明细胞环境对NPC的尺寸和结构有相当大的影响。人核孔复合体在其细胞环境中的结构揭示了显著扩张的中央通道，并显示其核质和细胞质环限制了通道尺寸并在内环处产生膜不对称性。
Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE). These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel. Here we use cryo-electron tomography on DLD-1 cells that were prepared using cryo-focused-ion-beam milling to generate a structural model for the human NPC in its native environment. We show that—compared with previous human NPC models obtained from purified NEs—the inner ring in our model is substantially wider; the volume of the central channel is increased by 75% and the nucleoplasmic and cytoplasmic rings are reorganized. Moreover, the NPC membrane exhibits asymmetry around the inner-ring complex. Using targeted degradation of Nup96, a scaffold nucleoporin of the cytoplasmic and nucleoplasmic rings, we observe the interdependence of each ring in modulating the central channel and maintaining membrane asymmetry. Our findings highlight the inherent flexibility of the NPC and suggest that the cellular environment has a considerable influence on NPC dimensions and architecture. Structure of human nuclear pore complex in its cellular environment reveals a substantially dilated central channel and shows that its nucleoplasmic and cytoplasmic rings restrict channel dimensions and create membrane asymmetry at the inner ring.
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影响因子：
64.8
作者：
Kim SJ;Fernandez-Martinez J;Nudelman I;Shi Y;Zhang W;Raveh B;Herricks T;Slaughter BD;Hogan JA;Upla P;Chemmama IE;Pellarin R;Echeverria I;Shivaraju M;Chaudhury AS;Wang J;Williams R;Unruh JR;Greenberg CH;Jacobs EY;Yu Z;de la Cruz MJ;Mironska R;Stokes DL;Aitchison JD;Jarrold MF;Gerton JL;Ludtke SJ;Akey CW;Chait BT;Sali A;Rout MP
通讯作者：
Rout MP
影响因子：
64.5
作者：
Knockenhauer KE;Schwartz TU
通讯作者：
Schwartz TU
影响因子：
5.7
作者：
Maimon, Tal;Elad, Nadav;Medalia, Ohad
通讯作者：
Medalia, Ohad
影响因子：
16.6
作者：
Eibauer, Matthias;Pellanda, Mauro;Turgay, Yagmur;Dubrovsky, Anna;Wild, Annik;Medalia, Ohad
通讯作者：
Medalia, Ohad
影响因子：
16.8
作者：
Kelley K;Knockenhauer KE;Kabachinski G;Schwartz TU
通讯作者：
Schwartz TU