Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, 69120 Heidelberg, Germany.
Science. 2021 Dec 10;374(6573):eabd9776. doi: 10.1126/science.abd9776.
In eukaryotic cells, nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes and mediate nucleocytoplasmic exchange. They are made of 30 different nucleoporins and form a cylindrical architecture around an aqueous central channel. This architecture is highly dynamic in space and time. Variations in NPC diameter have been reported, but the physiological circumstances and the molecular details remain unknown. Here, we combined cryo–electron tomography with integrative structural modeling to capture a molecular movie of the respective large-scale conformational changes in cellulo. Although NPCs of exponentially growing cells adopted a dilated conformation, they reversibly constricted upon cellular energy depletion or conditions of hypertonic osmotic stress. Our data point to a model where the nuclear envelope membrane tension is linked to the conformation of the NPC.
在真核细胞中,核孔复合体(NPC)融合了核内、外膜,并介导核质交换。它们由 30 种不同的核孔蛋白组成,并围绕着一个水相中央通道形成一个圆柱形的结构。这种结构在空间和时间上具有高度的动态性。已经报道了 NPC 直径的变化,但生理情况和分子细节仍不清楚。在这里,我们结合低温电子断层扫描和整合结构建模,在细胞内捕获了一个 NPC 大规模构象变化的分子电影。尽管指数生长期细胞的 NPC 采用了扩张构象,但在细胞能量耗竭或高渗渗透压胁迫条件下,它们会可逆地收缩。我们的数据表明,核膜张力与 NPC 的构象有关。