Intra-molecular cohesion of coils mediated by phenylalanine-glycine motifs in the natively unfolded domain of a nucleoporin

The nuclear pore complex (NPC) provides the sole aqueous conduit for macromolecular exchange between the nucleus and cytoplasm of cells. Its conduit contains a size-selective gate and is populated by a family of NPC proteins that feature long natively-unfolded domains with phenylalanine-glycine repeats. These FG nucleoporins play key roles in establishing the NPC permeability barrier, but little is known about their dynamic structure. Here we used molecular modeling and biophysical techniques to characterize the dynamic ensemble of structures of a representative FG domain from the yeast nucleoporin Nup116. The results show that its FG motifs function as intra-molecular cohesion elements that impart order to the FG domain. The cohesion of coils mediated by FG motifs in the natively unfolded domain of Nup116 supports a type of tertiary structure, a native pre-molten globule, that could become quaternary at the NPC through recruitment of neighboring FG nucleoporins, forming one cohesive meshwork of intertwined filaments capable of gating protein diffusion across the NPC by size exclusion