Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins

Journal Article · Wed Apr 02 00:00:00 EDT 2008 · Nat. Struct. Mol. Biol.

DOI:https://doi.org/10.1038/nsmb.1382· OSTI ID:1006522

Lok, Shee-Mei; Kostyuchenko, Victor; Nybakken, Grant E; Holdaway, Heather A; Battisti, Anthony J; Sukupolvi-Petty, Soila; Sedlak, Dagmar; Fremont, Daved H; Chipman, Paul R; Roehrig, John T; Diamond, Michael S; Kuhn, Richard J; Rossmann, Michael G ^[1]

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1. Purdue

The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1006522
• Journal Information: Nat. Struct. Mol. Biol., Vol. 15, Issue 2008; ISSN 1545-9993
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ANTIGENS
CRYSTAL STRUCTURE
DYNAMICS
GLYCOPROTEINS
HOST
IMAGES
MICROSCOPES
MOLECULES
MOTION
PROTEINS
SURFACES
UNITS