1.D.185. The Artificial Nuclear Pore Complex FG-NUP (FG-NUP) Family 

Nuclear Pore Complexes (NPCs) regulate bidirectional transport between the nucleus and the cytoplasm. FG nucleoporins (FG Nups) are intrinsically disordered proteins and are the putative regulators of nucleocytoplasmic transport. They allow fast, yet selective, transport of molecules through the nuclear pore complex. Intrinsically disordered FG-Nups line the NPC lumen and form a selective barrier, where transport of most proteins is inhibited whereas specific transporter proteins pass freely (Fragasso et al. 2021). The mechanism underlying selective transport through the NPC is not known. Fragasso et al. 2021 reconstituted the selective behaviour of the NPC bottom-up by introducing a rationally designed artificial FG-Nup that mimics natural Nups. They measured selective binding of the artificial FG-Nup brushes to the transport receptor Kap95 over cytosolic proteins such as BSA. Solid-state nanopores with the artificial FG-Nups lining their inner walls supported fast translocation of Kap95 while blocking BSA, thus demonstrating selectivity. Coarse-grained molecular dynamics simulations highlighted the formation of a selective meshwork with densities comparable to native NPCs. These findings reveal that simple design rules can recapitulate the selective behaviour of native FG-Nups and demonstrate that no specific spacer sequence nor a spatial segregation of different FG-motif types are needed to create selective NPCs.



Fragasso, A., H.W. de Vries, J. Andersson, E.O. van der Sluis, E. van der Giessen, A. Dahlin, P.R. Onck, and C. Dekker. (2021). A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex. Nat Commun 12: 2010.