Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system

Science. 2014 Feb 21;343(6173):881-5. doi: 10.1126/science.1247749. Epub 2014 Feb 6.


Flaviviruses, the human pathogens responsible for dengue fever, West Nile fever, tick-borne encephalitis, and yellow fever, are endemic in tropical and temperate parts of the world. The flavivirus nonstructural protein 1 (NS1) functions in genome replication as an intracellular dimer and in immune system evasion as a secreted hexamer. We report crystal structures for full-length, glycosylated NS1 from West Nile and dengue viruses. The NS1 hexamer in crystal structures is similar to a solution hexamer visualized by single-particle electron microscopy. Recombinant NS1 binds to lipid bilayers and remodels large liposomes into lipoprotein nanoparticles. The NS1 structures reveal distinct domains for membrane association of the dimer and interactions with the immune system and are a basis for elucidating the molecular mechanism of NS1 function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / chemistry
  • Cell Membrane / virology*
  • Crystallography, X-Ray
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / immunology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Immune System / chemistry
  • Immune System / virology*
  • Immunity, Innate
  • Lipid Bilayers
  • Microscopy, Electron
  • Protein Conformation
  • Protein Multimerization
  • Receptors, Immunologic
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / immunology


  • Lipid Bilayers
  • NS1 protein, Dengue virus type 2
  • Receptors, Immunologic
  • Viral Nonstructural Proteins
  • nonstructural protein 1, West Nile virus
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases

Associated data

  • PDB/4O6B
  • PDB/4O6C
  • PDB/4O6D