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

J Mol Biol. 2020 May 1;432(10):3353-3359. doi: 10.1016/j.jmb.2020.03.021. Epub 2020 Mar 25.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Nucleus / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Influenza A virus / enzymology*
  • Models, Molecular
  • Molecular Docking Simulation
  • Point Mutation*
  • Protein Binding
  • Protein Conformation
  • Protein Transport
  • RNA-Dependent RNA Polymerase / metabolism*
  • Viral Proteins / metabolism*
  • beta Karyopherins / chemistry*
  • beta Karyopherins / genetics

Substances

  • IPO5 protein, human
  • PA protein, influenza viruses
  • Viral Proteins
  • beta Karyopherins
  • RNA-Dependent RNA Polymerase