2R69

Crystal structure of Fab 1A1D-2 complexed with E-DIII of Dengue virus at 3.8 angstrom resolution

Summary for 2R69

• Entry DOI: 10.2210/pdb2r69/pdb
• Descriptor: Major envelope protein E, Heavy chain of 1A1D-2, Light chain of 1A1D-2 (3 entities in total)
• Functional Keywords: fab-antigen complex, capsid protein, cleavage on pair of basic residues, core protein, envelope protein, glycoprotein, membrane, transmembrane, virion, viral protein-immune system complex, viral protein/immune system
• Biological source: Dengue virus 2 Thailand/16681/84; More
• Cellular location: Peptide pr: Secreted . Small envelope protein M: Virion membrane ; Multi-pass membrane protein . Envelope protein E: Virion membrane ; Multi-pass membrane protein . Non-structural protein 1: Secreted : P18356
• Total number of polymer chains: 3
• Total formula weight: 57272.09

Authors

Lok, S.M.,Kostyuchenko, V.K.,Nybakken, G.E.,Holdaway, H.A.,Battisti, A.J.,Sukupolvi-petty, S.,Sedlak, D.,Fremont, D.H.,Chipman, P.R.,Roehrig, J.T.,Diamond, M.S.,Kuhn, R.J.,Rossmann, M.G. (deposition date: 2007-09-05, release date: 2007-12-25, Last modification date: 2018-01-24)

Primary citation

Lok, S.M.,Kostyuchenko, V.,Nybakken, G.E.,Holdaway, H.A.,Battisti, A.J.,Sukupolvi-Petty, S.,Sedlak, D.,Fremont, D.H.,Chipman, P.R.,Roehrig, J.T.,Diamond, M.S.,Kuhn, R.J.,Rossmann, M.G.
Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins.
Nat.Struct.Mol.Biol., 15:312-317, 2008

PubMed Abstract: 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.

PubMed: 18264114
DOI: 10.1038/nsmb.1382

Experimental method

X-RAY DIFFRACTION (3.8 Å)