title: Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes.
abstract: West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.
authors.affiliation: 266Department of Molecular Biophysics and Biochemistry, The Bass Center for Structural Biology, Yale University, 266 Whitney Ave., New Haven, Connecticut 06520, USA.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kanai
authors.forename: Kalipada
authors.initials: K
authors.lastname: Kar
authors.forename: Karen
authors.initials: K
authors.lastname: Anthony
authors.forename: L Hannah
authors.initials: LH
authors.lastname: Gould
authors.forename: Michel
authors.initials: M
authors.lastname: Ledizet
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Koski
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
mesh_terms: D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000737:chemistry; D004669:Encephalitis Viruses, Tick-Borne / Q000737:chemistry; D018604:Epitope Mapping; D000939:Epitopes; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology*; D014902:West Nile virus / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus