Architecture of the linker-scaffold in the nuclear pore

Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Although the arrangement of the structured scaffold nucleoporins in the NPC's symmetric core has been determined, their cohesion by multivalent unstructured linker nucleoporins has remained elusive. Combining biochemical reconstitution, high-resolution structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation, we elucidated the architecture of the evolutionarily conserved linker-scaffold, yielding a near-atomic composite structure of the human NPC's similar to 64-megadalton symmetric core. Whereas linkers generally play a rigidifying role, the linker-scaffold of the NPC provides the plasticity and robustness necessary for the reversible constriction and dilation of its central transport channel and the emergence of lateral channels. Our results substantially advance the structural characterization of the NPC symmetric core, providing a basis for future functional studies.