Journal: Cell Rep / Year: 2019 Title: Structural Basis for Neutralization and Protection by a Zika Virus-Specific Human Antibody. Authors: Lin Wang / Ruoke Wang / Lei Wang / Haijing Ben / Lei Yu / Fei Gao / Xuanling Shi / Chibiao Yin / Fuchun Zhang / Ye Xiang / Linqi Zhang / Abstract: 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 ...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.
H: heavy chain of Fab ZK2B10 L: light chain of Fab ZK2B10 E: Genome polyprotein K: heavy chain of Fab ZK2B10 I: light chain of Fab ZK2B10 F: Genome polyprotein
Mass: 25383.305 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#2: Antibody
lightchainofFabZK2B10
Mass: 22782.035 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#3: Protein
Genomepolyprotein
Mass: 10989.564 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zika virus / Production host: Escherichia coli K-12 (bacteria) / Strain (production host): K-12 / References: UniProt: A0A2Z2ESG6
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