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-Structure paper
Title | Neutralization mechanism of a highly potent antibody against Zika virus. |
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Journal, issue, pages | Nat Commun, Vol. 7, Page 13679, Year 2016 |
Publish date | Nov 24, 2016 |
Authors | Shuijun 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 Abstract | 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 ...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 links | Nat Commun / PubMed:27882950 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.0 - 12.0 Å |
Structure data | EMDB-9573, PDB-5h30: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRUS/IMMUNE SYSTEM / Antibody / VIRUS-IMMUNE SYSTEM complex / IgG NAG |