EMD-1418
Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins
EMD-1418
Single-particle24.0 Å
Deposition: 07/09/2007
Map released: 02/01/2008
Last modified: 10/10/2012
Sample Organism:
Dengue virus 2,
Mus musculus
Sample: Fab Fragment of MAb 1A1D-2 complexed with Dengue 2 virus
Fitted models: 2r6p (Avg. Q-score: 0.03)
Deposition Authors: Lok SM
Sample: Fab Fragment of MAb 1A1D-2 complexed with Dengue 2 virus
Fitted models: 2r6p (Avg. Q-score: 0.03)
Deposition Authors: Lok SM
Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins.
Lok SM ,
Kostyuchenko V ,
Nybakken GE,
Holdaway HA,
Battisti AJ,
Sukupolvi-Petty S,
Sedlak D,
Fremont DH ,
Chipman PR ,
Roehrig JT ,
Diamond MS,
Kuhn RJ,
Rossmann MG
(2008) Nat. Struct. Mol. Biol. , 15 , 312 - 317
(2008) Nat. Struct. Mol. Biol. , 15 , 312 - 317
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.
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.