Flavivirus NS1 Structures Reveal Surfaces for Associations with Membranes and the Immune System

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 s...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2014-02, Vol.343 (6173), p.881-885
Main Authors: 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.
Format: Article
Language:English
Subjects:
Amino acids
Binding sites
Cell Membrane - chemistry
Cell Membrane - virology
Crystal structure
Crystallography, X-Ray
Crystals
DEAD Box Protein 58
DEAD-box RNA Helicases - chemistry
DEAD-box RNA Helicases - immunology
dengue
Detergents
Dimers
Disulfides
Epitopes
fever
genome
glycosylation
human diseases
Humans
Hydrophobic and Hydrophilic Interactions
immune evasion
Immune system
Immune System - chemistry
Immune System - virology
Immunity, Innate
Lipid Bilayers
Liposomes
Membranes
Microscopy, Electron
Pathogens
Protein Conformation
Protein Multimerization
Proteins
Receptors, Immunologic
Structural Analysis (Linguistics)
Structural Analysis (Science)
vaccine development
viral nonstructural proteins
Viral Nonstructural Proteins - chemistry
Viral Nonstructural Proteins - immunology
Viruses
West Nile virus
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1247749