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

Christopher Swale (1, 2) , Bruno da Costa (3) , Laura Sedano (3) , Frederic Garzoni (4) , Andrew Mccarthy (2) , Imre Berger (2, 5) , Christoph Bieniossek (6) , Rob W H Ruigrok (1) , Bernard Delmas (3) , Thibaut Crépin (1)

1 IBS - UMR 5075 - Institut de biologie structurale
2 EMBL - European Molecular Biology Laboratory [Grenoble]
3 VIM (UR 0892) - Virologie et Immunologie Moléculaires
4 EMBL Grenoble - Laboratoire européen de biologie moléculaire - European Molecular Biology Laboratory
5 Max Planck-Bristol Centre for Minimal Biology
6 F. Hoffmann-La Roche [Basel]

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.

Mots clés: influenza polymerase assembly; NLS-binding site; PA-PB1 sub-complex nuclear import; host–pathogen interaction; human karyopherin

Domaines: Biologie structurale [q-bio.BM]

Christopher Swale, Bruno da Costa, Laura Sedano, Frederic Garzoni, Andrew Mccarthy, et al.. X-ray Structure of the Human Karyopherin RanBP5, an Essential Factor for Influenza Polymerase Nuclear Trafficking. Journal of Molecular Biology, 2020, 432 (10), pp.3353-3359. ⟨10.1016/j.jmb.2020.03.021⟩. ⟨hal-02555361⟩