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TitleStructural Basis for Neutralization and Protection by a Zika Virus-Specific Human Antibody.
Journal, issue, pagesCell Rep, Vol. 26, Issue 12, Page 3360-33368.e5, Year 2019
Publish dateMar 19, 2019
AuthorsLin Wang / Ruoke Wang / Lei Wang / Haijing Ben / Lei Yu / Fei Gao / Xuanling Shi / Chibiao Yin / Fuchun Zhang / Ye Xiang / Linqi Zhang /
PubMed AbstractWe previously reported a human monoclonal antibody, ZK2B10, capable of protection against Zika virus (ZIKV) infection and microcephaly in developing mouse embryos. Here, we report the structural ...We previously reported a human monoclonal antibody, ZK2B10, capable of protection against Zika virus (ZIKV) infection and microcephaly in developing mouse embryos. Here, we report the structural features and mechanism of action of ZK2B10. The crystal structure at a resolution of 2.32 Å revealed that the epitope is located on the lateral ridge of DIII of the envelope glycoprotein. Cryo-EM structure with mature ZIKV showed that the antibody binds to DIIIs around the icosahedral 2-fold, 3-fold, and 5-fold axes, a distinct feature compared to those reported for DIII-specific antibodies. The binding of ZK2B10 to ZIKV has no detectable effect on viral attachment to target cells or on conformational changes of the E glycoprotein in the acidic environment, suggesting that ZK2B10 functions at steps between the formation of the fusion intermediate and membrane fusion. These results provide structural and mechanistic insights into how ZK2B10 mediates protection against ZIKV infection.
External linksCell Rep / PubMed:30893607
MethodsEM (single particle) / X-ray diffraction
Resolution2.316 - 20.0 Å
Structure data

EMDB-9811, PDB-6jfh:
The asymmetric-reconstructed cryo-EM structure of Zika virus-FabZK2B10 complex
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-9812, PDB-6jfi:
The symmetric-reconstructed cryo-EM structure of Zika virus-FabZK2B10 complex
Method: EM (single particle) / Resolution: 11.0 Å

PDB-6jep:
Structure of a neutralizing antibody bound to the Zika envelope protein domain III
Method: X-RAY DIFFRACTION / Resolution: 2.316 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • zika virus
  • homo sapiens (human)
KeywordsANTIVIRAL PROTEIN / Antibody / complex / ZIKV / VIRUS

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