title: Crystal structure of the Japanese encephalitis virus envelope protein.
abstract: Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-Å resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimer in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Luca
authors.forename: Jad
authors.initials: J
authors.lastname: AbiMansour
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Nelson
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D018360:Crystallography, X-Ray; D019281:Dimerization; D004664:Encephalitis Virus, Japanese / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D004672:Encephalitis, Japanese / Q000821:virology; D018604:Epitope Mapping; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C080628:glycoprotein E, Japanese encephalitis virus