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

David L. Akey, W. Clay Brown, Somnath Dutta, Jamie Konwerski, Joyce Jose, Thomas J. Jurkiw, James DelProposto, Craig M. Ogata, Georgios Skiniotis, Richard J. Kuhn, Janet L. Smith

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)881-885
Number of pages5
JournalScience
Volume343
Issue number6173
DOIs
StatePublished - Jan 1 2014

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Flavivirus
Immune System
Membranes
Proteins
West Nile Fever
Tick-Borne Encephalitis
Yellow Fever
Immune Evasion
West Nile virus
Dengue Virus
Dengue
Lipid Bilayers
Recombinant Proteins
Liposomes
Nanoparticles
Lipoproteins
Electron Microscopy
Genome

All Science Journal Classification (ASJC) codes

  • General

Cite this

Akey, D. L., Brown, W. C., Dutta, S., Konwerski, J., Jose, J., Jurkiw, T. J., ... Smith, J. L. (2014). Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system. Science, 343(6173), 881-885. https://doi.org/10.1126/science.1247749
Akey, David L. ; Brown, W. Clay ; Dutta, Somnath ; Konwerski, Jamie ; Jose, Joyce ; Jurkiw, Thomas J. ; DelProposto, James ; Ogata, Craig M. ; Skiniotis, Georgios ; Kuhn, Richard J. ; Smith, Janet L. / Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system. In: Science. 2014 ; Vol. 343, No. 6173. pp. 881-885.
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Akey, DL, Brown, WC, Dutta, S, Konwerski, J, Jose, J, Jurkiw, TJ, DelProposto, J, Ogata, CM, Skiniotis, G, Kuhn, RJ & Smith, JL 2014, 'Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system', Science, vol. 343, no. 6173, pp. 881-885. https://doi.org/10.1126/science.1247749

Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system. / Akey, David L.; Brown, W. Clay; Dutta, Somnath; Konwerski, Jamie; Jose, Joyce; Jurkiw, Thomas J.; DelProposto, James; Ogata, Craig M.; Skiniotis, Georgios; Kuhn, Richard J.; Smith, Janet L.

In: Science, Vol. 343, No. 6173, 01.01.2014, p. 881-885.

Research output: Contribution to journalArticle

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