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

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Swale, Christopher | da Costa, Bruno | Sedano, Laura | Garzoni, Frederic | Mccarthy, Andrew | Berger, Imre | Bieniossek, Christoph | Ruigrok, Rob W H | Delmas, Bernard | Crépin, Thibaut

Edité par CCSD ; Elsevier -

International audience. 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.

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