Abstract

The nucleus must import each and every protein from the cytoplasm. On the other hand, nuclei produce and export tRNAs, mRNAs and ribosomes to the cytoplasm, where they function in translation. This nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs), which are embedded in the nuclear envelope and are equipped with a sieve-like permeability barrier. This barrier retains inert macromolecules while allowing the facilitated passage of nuclear transport receptors (NTRs), which in turn shuttle cargo into or out of the nucleus. Indeed, NPCs are highly efficient sorting machines, supporting ~1000 translocation events or a mass flow of 100 Megadaltons per second. FG repeat domains are key players in nuclear transport. They are intrinsically disordered, of low sequence complexity and contain numerous FG (phenylalanine-glycine) dipeptide motifs that bind NTRs during facilitated translocation. In addition, they can engage in multivalent ‘cohesive’ interactions to form the so-called FG phase, which acts as a permeability barrier within the central NPC channel. This FG phase repels inert macromolecules, preventing mixing of nuclear and cytoplasmic contents. At the same time, it is an excellent ‘solvent’ for NTRs, allowing them to pass rapidly with their cargo.

The lecture will focus on the assembly, properties and transport selectivity of the FG phase. It will address what ‘cohesive’ interactions are, which features of a mobile species encode a rapid or a slow pore-passage, how RNAs and ribosomal subunits are transported, and how the giant capsid of HIV can traverse nuclear pores and deliver the viral genome into the nucleus.