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TitleDENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.
Journal, issue, pagesScience, Vol. 349, Issue 6243, Page 88-91, Year 2015
Publish dateJul 3, 2015
AuthorsGuntur Fibriansah / Kristie D Ibarra / Thiam-Seng Ng / Scott A Smith / Joanne L Tan / Xin-Ni Lim / Justin S G Ooi / Victor A Kostyuchenko / Jiaqi Wang / Aravinda M de Silva / Eva Harris / James E Crowe / Shee-Mei Lok /
PubMed AbstractThere 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. ...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.
External linksScience / PubMed:26138979 / PubMed Central
MethodsEM (single particle)
Resolution6.5 - 23.0 Å
Structure data

EMDB-2967, PDB-4uif:
Cryo-EM structure of Dengue virus serotype 2 in complex with antigen-binding fragments of human antibody 2D22
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-2968, PDB-4uih:
Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C complexed with human antibody 2D22 Fab at 37 degree C. The Fab molecules were added to the virus before 37 degree C incubation.
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-2969:
Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C complexed with human antibody 2D22 Fab at 37 degree C. The Fab molecules were added to virus that was pre-incubated at 37 degree C.
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-2996: Cryo-EM structure of Dengue virus serotype 2 strain PVP94/07 complexed with human antibody 2D22 Fab at 37 degrees C
PDB-5a1z: Cryo-EM structure of Dengue virus serotype 2 strain PVP94-07 complexed with human antibody 2D22 Fab at 37 degrees C
Method: EM (single particle) / Resolution: 6.9 Å

EMDB-2997:
Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C complexed with human antibody 2D22 Fab at 4 degrees C
Method: EM (single particle) / Resolution: 13.0 Å

EMDB-2998:
Cryo-EM structure of the unexpanded particles of Dengue virus serotype 2 strain New Guinea-C in complex with human antibody 2D22 Fab at 37 degrees C. The Fab molecules were added to the virus that had been pre-incubated at 37 degrees C.
Method: EM (single particle) / Resolution: 11.0 Å

EMDB-2999:
Cryo-EM structure of the unexpanded particles of Dengue virus serotype 2 strain New Guinea-C in complex with human antibody 2D22 Fab at 37 degrees C. The Fab molecules were added to the virus before 37 degrees C incubation.
Method: EM (single particle) / Resolution: 23.0 Å

Source
  • homo sapiens (human)
  • dengue virus 2
KeywordsVIRAL PROTEIN / DENGUE VIRUS / HUMAN ANTIBODY / CRYO-EM / NEUTRALIZATION / DENGUE SEROTYPE 2 / VIRUS

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