EMD-2997

Single-particle
13.0 Å
EMD-2997 Deposition: 07/05/2015
Map released: 15/07/2015
Last modified: 15/07/2015
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-2997

Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C complexed with human antibody 2D22 Fab at 4 degrees C

EMD-2997

Single-particle
13.0 Å
EMD-2997 Deposition: 07/05/2015
Map released: 15/07/2015
Last modified: 15/07/2015
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Dengue virus serotype 2 strain New Guinea-C complexed with Fab fragments of human antibody 2D22.

Deposition Authors: Fibriansah G , Ibarra KD, Ng TS, Smith SA, Tan JL, Lim XN , Ooi JSG , Kostyuchenko VA , Wang J , de Silva AM, Harris E, Crowe JE , Lok SM
DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.
Abstract:
There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.