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-particle13.0 Å
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Map released: 15/07/2015
Last modified: 15/07/2015
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
Sample: Dengue virus serotype 2 strain New Guinea-C complexed with Fab fragments of human antibody 2D22.
Deposition Authors: Fibriansah G
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DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.
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
(2015) Science , 349 , 88 - 91
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(2015) Science , 349 , 88 - 91
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.
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.