Efficiency, selectivity and robustness of the nuclear pore complex transport

Abstract

All materials enter or exit the cell nucleus through nuclear pore complexes (NPCs), efficient transport devices that combine high selectivity and throughput. A central feature of this transport is the binding of cargo-carrying soluble transport factors to flexible, unstructured proteinaceous filaments called FG-nups that line the NPC. We have modeled the dynamics of transport factors and their interaction with the flexible FG-nups as diffusion in an effective potential, using both analytical theory and computer simulations. We show that specific binding of transport factors to the FG-nups facilitates transport and provides the mechanism of selectivity. We show that the high selectivity of transport can be accounted for by competition for both binding sites and space inside the NPC, which selects for transport factors over other macromolecules that interact only non-specifically with the NPC. We also show that transport is relatively insensitive to changes in the number and distribution of FG-nups in the NPC, due mainly to their flexibility; this accounts for recent experiments where up to half of the total mass of the NPC has been deleted, without abolishing the transport. Notably, we demonstrate that previously established physical and structural properties of the NPC can account for observed features of nucleocytoplasmic transport. Finally, our results suggest strategies for creation of artificial nano-molecular sorting devices.Comment: 38 pages, six figure