title: Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins.
abstract: The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.
authors.affiliation: Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, Indiana 47907-2054, USA.
authors.forename: Shee-Mei
authors.initials: SM
authors.lastname: Lok
authors.forename: Victor
authors.initials: V
authors.lastname: Kostyuchenko
authors.forename: Grant E
authors.initials: GE
authors.lastname: Nybakken
authors.forename: Heather A
authors.initials: HA
authors.lastname: Holdaway
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Battisti
authors.forename: Soila
authors.initials: S
authors.lastname: Sukupolvi-Petty
authors.forename: Dagmar
authors.initials: D
authors.lastname: Sedlak
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: Paul R
authors.initials: PR
authors.lastname: Chipman
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure; D009500:Neutralization Tests; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins