Sorting with Disorder at Nuclear Pores

Abstract

Macromolecular traffic between the nucleus and cytoplasm of cells is mediated by karyopherins and is gated at nuclear pores (NPCs) by intrinsically-disordered proteins featuring phenylalanine-glycine repeats: the FG nucleoporins. Despite their dynamic nature, these FG nups adopt distinct categories of disordered structure with unique functions. Some are collapsed-coil globules that stick to each via FG repeats, and others are highly-extended coils that repel each other. Remarkably, these structures are segregated within FG nups and at NPCs to create a quaternary gating structure that appears suspended in the middle of the nuclear pore termed the transporter or plug. We describe how this ‘ghostly’ structure, whose existence has been debated for decades, is naturally-formed by more than one hundred intrinsically-disordered proteins acting collectively. We will also discuss how the distinct categories of disordered nup structures serve different functions in karyopherin-mediated transport.