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https://doi.org/10.1002/emmm.201303404
Title: | A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface | Authors: | Fibriansah G. Tan J.L. Smith S.A. de Alwis A.R. Ng T.-S. Kostyuchenko V.A. Ibarra K.D. Wang J. Harris E. de Silva A. Crowe J.E. Lok S.-M. |
Keywords: | CD209 antigen epitope genomic RNA human monoclonal antibody human monoclonal antibody 1F4 immunoglobulin F(ab) fragment immunoglobulin G immunoglobulin G1 membrane protein neutralizing antibody unclassified drug virus envelope protein virus receptor amino acid sequence animal experiment animal model animal tissue article bone marrow cell cell strain U937 complementarity determining region conformation controlled study cryoelectron microscopy dengue Dengue virus Dengue virus 1 Dengue virus 2 Dengue virus 3 Dengue virus 4 enzyme linked immunosorbent assay gene dosage glycosylation heavy chain hinge region human hydrogen bond in vitro study in vivo study lethal dose light chain limit of detection mature virus mouse nonhuman priority journal protein assembly protein conformation protein quaternary structure protein secondary structure receptor binding sequence alignment serodiagnosis serotype sublethal dose Vero cell virus attachment virus entry virus load virus morphology virus neutralization Amino Acid Sequence Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Cell Line Dengue Dengue Virus Epitopes Humans Immunoglobulin Fab Fragments Mice Molecular Dynamics Simulation Molecular Sequence Data Protein Structure, Tertiary Viral Envelope Proteins Virus Internalization |
Issue Date: | 2014 | Citation: | Fibriansah G., Tan J.L., Smith S.A., de Alwis A.R., Ng T.-S., Kostyuchenko V.A., Ibarra K.D., Wang J., Harris E., de Silva A., Crowe J.E., Lok S.-M. (2014). A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. EMBO Molecular Medicine 6 (3) : 358-371. ScholarBank@NUS Repository. https://doi.org/10.1002/emmm.201303404 | Abstract: | Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection. © 2014 The Authors. | Source Title: | EMBO Molecular Medicine | URI: | https://scholarbank.nus.edu.sg/handle/10635/174171 | ISSN: | 17574676 | DOI: | 10.1002/emmm.201303404 |
Appears in Collections: | Elements Staff Publications |
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