title: Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system.
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.
authors: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors: David L
authors: DL
authors: Akey
authors: W Clay
authors: WC
authors: Brown
authors: Somnath
authors: S
authors: Dutta
authors: Jamie
authors: J
authors: Konwerski
authors: Joyce
authors: J
authors: Jose
authors: Thomas J
authors: TJ
authors: Jurkiw
authors: James
authors: J
authors: DelProposto
authors: Craig M
authors: CM
authors: Ogata
authors: Georgios
authors: G
authors: Skiniotis
authors: Richard J
authors: RJ
authors: Kuhn
authors: Janet L
authors: JL
authors: Smith
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000821:virology*; D018360:Crystallography, X-Ray; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000276:immunology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007107:Immune System / Q000737:chemistry / Q000821:virology*; D007113:Immunity, Innate; D008051:Lipid Bilayers; D008854:Microscopy, Electron; D011487:Protein Conformation; D055503:Protein Multimerization; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000276:immunology
chemical_list: D008051:Lipid Bilayers; C079340:NS1 protein, Dengue virus type 2; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins; C531936:nonstructural protein 1, West Nile virus; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases