CBS (Centre de Biologie Structurale), Univ Montpellier, CNRS, INSERM, Montpellier, France.
MRI, Biocampus, University of Montpellier, CNRS, INSERM, Montpellier, France.
Nanoscale. 2023 Mar 23;15(12):5756-5770. doi: 10.1039/d2nr06034e.
Nuclear pore complexes (NPCs) are the only gateways between the nucleus and cytoplasm in eukaryotic cells. They restrict free diffusion to molecules below 5 nm while facilitating the active transport of selected cargoes, sometimes as large as the pore itself. This versatility implies an important pore plasticity. Recently, cryo-EM and AI-based protein modeling of human NPC revealed with acute precision how most constituents are arranged. But the basket, a fish trap-like structure capping the nucleoplasmic side of the pore, remains poorly resolved. Here by atomic force microscopy (AFM) coupled to single molecule localization microscopy (SMLM) we revealed that the basket is very soft and explores a large conformational landscape: apart from its canonical basket shape, it dives into the central pore channel or opens, with filaments reaching to the pore sides. Our observations highlight how this structure can adapt and let morphologically diverse cargoes shuttle through NPCs.
核孔复合体（NPC）是真核细胞中核与细胞质之间唯一的通道。它们限制了直径小于 5nm 的分子的自由扩散，同时促进了选定货物的主动运输，有时货物的大小与孔本身一样大。这种多功能性意味着 NPC 具有重要的柔韧性。最近，基于冷冻电镜和人工智能的人类 NPC 蛋白建模以极高的精度揭示了大多数组成部分的排列方式。但是，位于核质侧的篮状结构仍然解析度较差。在这里，我们通过原子力显微镜（AFM）结合单分子定位显微镜（SMLM）发现，篮状结构非常柔软，可以探索到一个很大的构象景观：除了其典型的篮状形状外，它还可以深入到中央孔道中，或者打开，使纤维延伸到孔的侧面。我们的观察结果强调了这种结构如何适应并允许形态多样的货物穿梭通过 NPC。
