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TitleNeutralization mechanism of a highly potent antibody against Zika virus.
Journal, issue, pagesNat Commun, Vol. 7, Page 13679, Year 2016
Publish dateNov 24, 2016
AuthorsShuijun Zhang / Victor A Kostyuchenko / Thiam-Seng Ng / Xin-Ni Lim / Justin S G Ooi / Sebastian Lambert / Ter Yong Tan / Douglas G Widman / Jian Shi / Ralph S Baric / Shee-Mei Lok /
PubMed AbstractThe rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies ...The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event-a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate.
External linksNat Commun / PubMed:27882950 / PubMed Central
MethodsEM (single particle)
Resolution4.0 - 12.0 Å
Structure data

9573

5h30

EMDB-9573, PDB-5h30:
Cryo-EM structure of zika virus complexed with Fab C10 at pH 6.5
Method: EM (single particle) / Resolution: 4.4 Å

9574

5h32

EMDB-9574, PDB-5h32:
Cryo-EM structure of zika virus complexed with Fab C10 at pH 5.0
Method: EM (single particle) / Resolution: 12.0 Å

9575

5h37

EMDB-9575, PDB-5h37:
Cryo-EM structure of zika virus complexed with Fab C10 at pH 8.0
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • zika virus
  • ZIKV (virus)
  • homo sapiens (human)
KeywordsVIRUS/IMMUNE SYSTEM / Antibody / VIRUS-IMMUNE SYSTEM complex / IgG NAG

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