Improving the hole picture: towards a consensus on the mechanism of nuclear transport

Nuclear pore complexes (NPCs) mediate the exchange of materials between the nucleo-plasm and cytoplasm, playing a key role in the separation of nucleic acids and proteins into their required compartments. The static structure of the NPC is relatively well defined by recent cryo-EM and other studies. The functional roles of dynamic compo-nents in the pore of the NPC, phenylalanyl-glycyl (FG) repeat rich nucleoporins, is less clear because of our limited understanding of highly dynamic protein systems. These proteins form a 'restrained concentrate' which interacts with and concentrates nuclear transport factors (NTRs) to provide facilitated nucleocytoplasmic transport of cargoes. Very rapid on-and off-rates among FG repeats and NTRs supports extremely fast facili-tated transport, close to the rate of macromolecular diffusion in cytoplasm, while com-plexes without specific interactions are entropically excluded, though details on several aspects of the transport mechanism and FG repeat behaviors remain to be resolved. However, as discussed here, new technical approaches combined with more advanced modeling methods will likely provide an improved dynamic description of NPC transport, potentially at the atomic level in the near future. Such advances are likely to be of major benefit in comprehending the roles the malfunctioning NPC plays in cancer, ageing, viral diseases, and neurodegeneration.

Automated summary

Nuclear pore complexes (NPCs) play a crucial role in material exchange between the nucleus and cytoplasm, with a specific focus on nucleic acids and proteins. While the static structure of NPCs has been well defined, the functional roles of certain dynamic components, such as phenylalanyl-glycyl (FG) repeat rich nucleoporins, remain unclear. However, advancements in technical approaches and modeling methods may soon provide a more accurate and detailed understanding of NPC transport, potentially at the atomic level. Such progress would be invaluable in comprehending the impact of malfunctioning NPCs in various diseases.