Unknown

Dataset Information

0

Potent dengue virus neutralization by a therapeutic antibody with low monovalent affinity requires bivalent engagement.


ABSTRACT: We recently described our most potently neutralizing monoclonal antibody, E106, which protected against lethal Dengue virus type 1 (DENV-1) infection in mice. To further understand its functional properties, we determined the crystal structure of E106 Fab in complex with domain III (DIII) of DENV-1 envelope (E) protein to 2.45 Å resolution. Analysis of the complex revealed a small antibody-antigen interface with the epitope on DIII composed of nine residues along the lateral ridge and A-strand regions. Despite strong virus neutralizing activity of E106 IgG at picomolar concentrations, E106 Fab exhibited a ?20,000-fold decrease in virus neutralization and bound isolated DIII, E, or viral particles with only a micromolar monovalent affinity. In comparison, E106 IgG bound DENV-1 virions with nanomolar avidity. The E106 epitope appears readily accessible on virions, as neutralization was largely temperature-independent. Collectively, our data suggest that E106 neutralizes DENV-1 infection through bivalent engagement of adjacent DIII subunits on a single virion. The isolation of anti-flavivirus antibodies that require bivalent binding to inhibit infection efficiently may be a rare event due to the unique icosahedral arrangement of envelope proteins on the virion surface.

SUBMITTER: Edeling MA 

PROVIDER: S-EPMC3990716 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications


We recently described our most potently neutralizing monoclonal antibody, E106, which protected against lethal Dengue virus type 1 (DENV-1) infection in mice. To further understand its functional properties, we determined the crystal structure of E106 Fab in complex with domain III (DIII) of DENV-1 envelope (E) protein to 2.45 Å resolution. Analysis of the complex revealed a small antibody-antigen interface with the epitope on DIII composed of nine residues along the lateral ridge and A-strand r  ...[more]

Similar Datasets

| S-EPMC7935256 | biostudies-literature
| S-EPMC3242841 | biostudies-literature
| S-EPMC5997965 | biostudies-literature
| S-EPMC7301900 | biostudies-literature
| S-EPMC7591918 | biostudies-literature
| S-EPMC3236064 | biostudies-literature
| S-EPMC5627287 | biostudies-literature
| S-EPMC27086 | biostudies-literature
| S-EPMC8758676 | biostudies-literature
| S-EPMC6964813 | biostudies-literature