These Nups assemble into sub-complexes that form higher-order structures called spokes. Eight spokes assemble into even larger, discrete and relatively rigid modules: coaxial outer and inner rings form a symmetric core scaffold at the heart of which are sturdy diagonal columns. This scaffold is connected to a membrane ring and two peripheral assemblies, a nuclear basket and a cytoplasmic RNP export platform, all of which are. Remarkably, flexible connectors run the entire length of each spoke, tying together every major element in the NPC.
They link the periphery and outer rings to the inner rings, both inner rings to the pore membrane and adjacent spokes to one another. This combination of rigid modules held together by flexible connectors appears to imbue the structure with both strength and flexibility, being reminiscent of a suspension bridge, in which rigid supporting columns are firmly anchored to a substrate and flexible suspension cables connect the columns and roadway to provide a strong and resilient structure. The scaffold surrounds a central channel that is formed in part by nucleoporins termed FG Nups, from which multiple intrinsically disordered Phe-Gly (FG) repeat motifs project, contributing to a central density termed the central transporter. These FG motifs mediate selective nucleocytoplasmic transport through specific interactions with nuclear transport factors. The structured regions of the NPC largely direct the FG-repeat regions inwards toward the axis of the central channel, instead of projecting from the NPC towards the cytoplasm and nucleoplasm as they are often represented. This geometry generates a highly concentrated and dynamic FG-repeat phase through which cargo-carrying transport factors readily pass, facilitated by their specific FG interactions, whereas nonspecific macromolecular diffusion is hindered by this same dense phase. Our map also shows that the entire export platform positions the cytoplasmic mRNA export factor docking sites and messenger ribonucleoprotein (mRNP) remodeling machinery right over the NPC’s central channel rather than on distal cytoplasmic filaments, as previously supposed. We suggest that this configuration efficiently captures and remodels exporting mRNP particles immediately upon reaching the cytoplasmic side of the NPC.