title: Structure of the dengue virus envelope protein after membrane fusion.
abstract: Dengue virus enters a host cell when the viral envelope glycoprotein, E, binds to a receptor and responds by conformational rearrangement to the reduced pH of an endosome. The conformational change induces fusion of viral and host-cell membranes. A three-dimensional structure of the soluble E ectodomain (sE) in its trimeric, postfusion state reveals striking differences from the dimeric, prefusion form. The elongated trimer bears three 'fusion loops' at one end, to insert into the host-cell membrane. Their structure allows us to model directly how these fusion loops interact with a lipid bilayer. The protein folds back on itself, directing its carboxy terminus towards the fusion loops. We propose a fusion mechanism driven by essentially irreversible conformational changes in E and facilitated by fusion-loop insertion into the outer bilayer leaflet. Specific features of the folded-back structure suggest strategies for inhibiting flavivirus entry.
authors.affiliation: Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
authors.forename: Steven
authors.initials: S
authors.lastname: Ogata
authors.forename: David
authors.initials: D
authors.lastname: Clements
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
mesh_terms: D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion; D008854:Microscopy, Electron; D008954:Models, Biological; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C051821:E-glycoprotein, Dengue virus type 2; D008081:Liposomes; D014759:Viral Envelope Proteins