2R29

Neutralization of dengue virus by a serotype cross-reactive antibody elucidated by cryoelectron microscopy and x-ray crystallography

Summary for 2R29

• Entry DOI: 10.2210/pdb2r29/pdb
• Descriptor: Envelope protein E, Heavy chain of Fab 1A1D-2, Light chain of Fab 1A1D-2, ... (4 entities in total)
• Functional Keywords: fab-antigen complex, atp-binding, capsid protein, cleavage on pair of basic residues, endoplasmic reticulum, envelope protein, glycoprotein, helicase, hydrolase, membrane, metal-binding, multifunctional enzyme, nucleotide-binding, nucleotidyltransferase, nucleus, phosphorylation, protease, ribonucleoprotein, rna replication, rna-binding, rna-directed rna polymerase, secreted, serine protease, transcription, transcription regulation, transferase, transmembrane, viral nucleoprotein, virion, viral protein-immune system complex, viral protein/immune system
• Biological source: Dengue virus 2 Thailand/16681/84; More
• Cellular location: Capsid protein C: Virion . 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 . Non-structural protein 2A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P14340
• Total number of polymer chains: 3
• Total formula weight: 57970.86

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: 2007-08-24, release date: 2007-12-25, Last modification date: 2024-11-20)

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 Å)