X-ray Structure of the Human Karyopherin RanBP5, an Essential Factor for Influenza Polymerase Nuclear Trafficking

Here, we describe the crystal structures of two distinct isoforms of ligand-free human karyopherin RanBP5 and investigate its global propensity to interact with influenza A virus polymerase. Our results confirm the general architecture and mechanism of the IMB3 karyopherin-β subfamily whilst also highlighting differences with the yeast orthologue Kap121p. Moreover, our results provide insight into the structural flexibility of β-importins in the unbound state. Based on docking of a nuclear localisation sequence, point mutations were designed, which suppress influenza PA-PB1 subcomplex binding to RanBP5 in a binary protein complementation assay. [Display omitted] •RanBP5, by importing PA-PB1 polymerase sub-complex in the nucleus of the infected cells, is an essential factor of influenza virus infection.•The two isoform structures of human karyopherin RanBP5 illustrate its inherent dynamics.•We identify the NLS-binding site in RanBP5.•Using a binary protein complementation assay, we can suppress influenza PA-PB1 subcomplex interaction with RanBP5.