ジャーナル: Science / 年: 2015 タイトル: DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers. 著者: Guntur Fibriansah / Kristie D Ibarra / Thiam-Seng Ng / Scott A Smith / Joanne L Tan / Xin-Ni Lim / Justin S G Ooi / Victor A Kostyuchenko / Jiaqi Wang / Aravinda M de Silva / Eva Harris / ...著者: Guntur Fibriansah / Kristie D Ibarra / Thiam-Seng Ng / Scott A Smith / Joanne L Tan / Xin-Ni Lim / Justin S G Ooi / Victor A Kostyuchenko / Jiaqi Wang / Aravinda M de Silva / Eva Harris / James E Crowe / Shee-Mei Lok / 要旨: There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. ...There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.
全体 : Dengue virus serotype 2 strain New Guinea-C complexed with Fab fr...
全体
名称: Dengue virus serotype 2 strain New Guinea-C complexed with Fab fragments of human antibody 2D22.
要素
試料: Dengue virus serotype 2 strain New Guinea-C complexed with Fab fragments of human antibody 2D22.
ウイルス: Dengue Virus serotype 2 (デング熱ウイルス)
タンパク質・ペプチド: Antigen-binding fragment of human antibody 2D22
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超分子 #1000: Dengue virus serotype 2 strain New Guinea-C complexed with Fab fr...
超分子
名称: Dengue virus serotype 2 strain New Guinea-C complexed with Fab fragments of human antibody 2D22. タイプ: sample / ID: 1000 / Number unique components: 2
分子 #1: Antigen-binding fragment of human antibody 2D22
分子
名称: Antigen-binding fragment of human antibody 2D22 / タイプ: protein_or_peptide / ID: 1 詳細: 180 copies of Fab 2D22 molecule bind to virus surface コピー数: 180 / 組換発現: No
由来(天然)
生物種: Homo sapiens (ヒト) / 別称: Human / 細胞: memory B-cell
分子量
理論値: 50 KDa
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実験情報
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構造解析
手法
クライオ電子顕微鏡法
解析
単粒子再構成法
試料の集合状態
particle
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試料調製
緩衝液
pH: 8 / 詳細: 10 mM Tris-HCl pH 8.0, 120 mM NaCl and 1 mM EDTA
グリッド
詳細: ultra-thin carbon-coated lacey carbon grid
凍結
凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV 手法: blotted with filter paper for 2 seconds prior to snap freezing
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
日付
2014年3月28日
撮影
カテゴリ: CCD フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 実像数: 87 / 平均電子線量: 18 e/Å2