2R29

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

2R29 の概要

• エントリーDOI: 10.2210/pdb2r29/pdb
• 分子名称: Envelope protein E, Heavy chain of Fab 1A1D-2, Light chain of Fab 1A1D-2, ... (4 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Dengue virus 2 Thailand/16681/84; 詳細
• 細胞内の位置: 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
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 57970.86

構造登録者

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. (登録日: 2007-08-24, 公開日: 2007-12-25, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)