Structural analysis of the complex between influenza B nucleoprotein and human importin-α

Sci Rep. 2017 Dec 7;7(1):17164. doi: 10.1038/s41598-017-17458-z.

Abstract

Influenza viruses are negative strand RNA viruses that replicate in the nucleus of the cell. The viral nucleoprotein (NP) is the major component of the viral ribonucleoprotein. In this paper we show that the NP of influenza B has a long N-terminal tail of 70 residues with intrinsic flexibility. This tail contains the Nuclear Location Signal (NLS). The nuclear trafficking of the viral components mobilizes cellular import factors at different stages, making these host-pathogen interactions promising targets for new therapeutics. NP is imported into the nucleus by the importin-α/β pathway, through a direct interaction with importin-α isoforms. Here we provide a combined nuclear magnetic resonance and small-angle X-ray scattering (NMR/SAXS) analysis to describe the dynamics of the interaction between influenza B NP and the human importin-α. The NP of influenza B does not have a single NLS nor a bipartite NLS but our results suggest that the tail harbors several adjacent NLS sequences, located between residues 30 and 71.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nucleocapsid Proteins
  • Protein Binding
  • Protein Conformation*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Scattering, Small Angle
  • Viral Core Proteins / chemistry*
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism*
  • alpha Karyopherins / chemistry*
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*

Substances

  • KPNA6 protein, human
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • RNA-Binding Proteins
  • Viral Core Proteins
  • alpha Karyopherins