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TitleA highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins.
Journal, issue, pagesNat Commun, Vol. 6, Page 6341, Year 2015
Publish dateFeb 20, 2015
AuthorsGuntur Fibriansah / Joanne L Tan / Scott A Smith / Ruklanthi de Alwis / Thiam-Seng Ng / Victor A Kostyuchenko / Ramesh S Jadi / Petra Kukkaro / Aravinda M de Silva / James E Crowe / Shee-Mei Lok /
PubMed AbstractDengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue ...Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue infection consists of highly neutralizing antibodies. Here we show that the DENV-specific human monoclonal antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. The 9 Å resolution cryo-electron microscopy structure of the Fab 5J7-DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the antibody to fully coat the virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. Our study reveals a highly efficient and unusual mechanism of molecular recognition by an antibody.
External linksNat Commun / PubMed:25698059 / PubMed Central
MethodsEM (single particle)
Resolution6.0 - 9.0 Å
Structure data

5933

3j6s

EMDB-5933: Cryo-EM structure of Dengue serotype 3 virus at 28 degrees C
PDB-3j6s: Cryo-EM structure of Dengue virus serotype 3 at 28 degrees C
Method: EM (single particle) / Resolution: 6.0 Å

5934

3j6t

EMDB-5934: Cryo-EM structure of Dengue serotype 3 virus at 37 degrees C
PDB-3j6t: Cryo-EM structure of Dengue virus serotype 3 at 37 degrees C
Method: EM (single particle) / Resolution: 7.0 Å

5935

3j6u

EMDB-5935, PDB-3j6u:
Cryo-EM structure of Dengue virus serotype 3 in complex with human antibody 5J7 Fab
Method: EM (single particle) / Resolution: 9.0 Å

Source
  • homo sapiens (human)
  • dengue virus 3
KeywordsVIRUS / Dengue virus / VIRUS/IMMUNE SYSTEM / human antibody / neutralization / VIRUS-IMMUNE SYSTEM complex

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