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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
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
bone marrow cell
cell strain U937
complementarity determining region
controlled study
cryoelectron microscopy
Dengue virus
Dengue virus 1
Dengue virus 2
Dengue virus 3
Dengue virus 4
enzyme linked immunosorbent assay
gene dosage
heavy chain
hinge region
hydrogen bond
in vitro study
in vivo study
lethal dose
light chain
limit of detection
mature virus
priority journal
protein assembly
protein conformation
protein quaternary structure
protein secondary structure
receptor binding
sequence alignment
sublethal dose
Vero cell
virus attachment
virus entry
virus load
virus morphology
virus neutralization
Amino Acid Sequence
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Cell Line
Dengue Virus
Immunoglobulin Fab Fragments
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.
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
ISSN: 17574676
DOI: 10.1002/emmm.201303404
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