Functional principles of the permeability barrier that guards vertebrate nuclear pore complexes

Nuclear pore complexes (NPCs) are giant macromolecular assemblies that are embeddedinto the double membrane of the nuclear envelope and control the transport processes between nucleus and cytoplasm. Vertebrate NPCs are composed of approximately 30 different nucleoporins, each present in multiple copies per pore. About one third of the nucleoporins contain characteristic Phe-Gly (FG) enriched domains on their N- or/and Ctermini. These FG domains are intrinsically unstructured protein stretches. In higher eukaryotes, they are typically modified at Ser/Thr residues by GlcNAc moieties. It is thought that nucleoporin FG repeat domains constitute the permeability barrier of NPCs. This barrier restricts passive diffusion of inert molecules larger than 20-40 kDa, but at the same time allows facilitated passage of selected substances, whose mass can reach several megadaltons. Nuclear transport receptors (NTRs) bind FG repeat domains and mediate facilitated translocation of cargo molecules through the permeability barrier of NPCs. […]