  Nuclear pore complexes (NPCs) mediate the exchange of materials between the
nucleoplasm 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 components 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 exchange among FG repeats and NTRs supports extremely fast
facilitated transport, close to the rate of macromolecular diffusion in
cytoplasm, while complexes 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,
aging, viral diseases, and neurodegeneration.
