ジャーナル: J Virol / 年: 2013 タイトル: Obstruction of dengue virus maturation by Fab fragments of the 2H2 antibody. 著者: Zhiqing Wang / Long Li / Janice G Pennington / Ju Sheng / Moh Lan Yap / Pavel Plevka / Geng Meng / Lei Sun / Wen Jiang / Michael G Rossmann / 要旨: The 2H2 monoclonal antibody recognizes the precursor peptide on immature dengue virus and might therefore be a useful tool for investigating the conformational change that occurs when the immature ...The 2H2 monoclonal antibody recognizes the precursor peptide on immature dengue virus and might therefore be a useful tool for investigating the conformational change that occurs when the immature virus enters an acidic environment. During dengue virus maturation, spiky, immature, noninfectious virions change their structure to form smooth-surfaced particles in the slightly acidic environment of the trans-Golgi network, thereby allowing cellular furin to cleave the precursor-membrane proteins. The dengue virions become fully infectious when they release the cleaved precursor peptide upon reaching the neutral-pH environment of the extracellular space. Here we report on the cryo-electron microscopy structures of the immature virus complexed with the 2H2 antigen binding fragments (Fab) at different concentrations and under various pH conditions. At neutral pH and a high concentration of Fab molecules, three Fab molecules bind to three precursor-membrane proteins on each spike of the immature virus. However, at a low concentration of Fab molecules and pH 7.0, only two Fab molecules bind to each spike. Changing to a slightly acidic pH caused no detectable change of structure for the sample with a high Fab concentration but caused severe structural damage to the low-concentration sample. Therefore, the 2H2 Fab inhibits the maturation process of immature dengue virus when Fab molecules are present at a high concentration, because the three Fab molecules on each spike hold the precursor-membrane molecules together, thereby inhibiting the normal conformational change that occurs during maturation.
ダウンロード / ファイル: emd_5674.map.gz / 形式: CCP4 / 大きさ: 51.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Reconstruction of immature Dengue virus complexed with high-concentration 2H2 Fab at pH 7
ボクセルのサイズ
X=Y=Z: 3.72 Å
密度
表面レベル
By EMDB: 2.0 / ムービー #1: 3
最小 - 最大
-4.58107519 - 13.34346676
平均 (標準偏差)
0.61698598 (±1.8204031)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
-120
-120
-120
サイズ
240
240
240
Spacing
240
240
240
セル
A=B=C: 892.8 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
3.72
3.72
3.72
M x/y/z
240
240
240
origin x/y/z
0.000
0.000
0.000
length x/y/z
892.800
892.800
892.800
α/β/γ
90.000
90.000
90.000
MAP C/R/S
1
2
3
start NC/NR/NS
-120
-120
-120
NC/NR/NS
240
240
240
D min/max/mean
-4.581
13.343
0.617
-
添付データ
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試料の構成要素
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全体 : High-concentration Fab Fragment of 2H2 antibody binding to immatu...
全体
名称: High-concentration Fab Fragment of 2H2 antibody binding to immature Dengue virus at pH 7
要素
試料: High-concentration Fab Fragment of 2H2 antibody binding to immature Dengue virus at pH 7
ウイルス: Dengue virus (デング熱ウイルス)
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超分子 #1000: High-concentration Fab Fragment of 2H2 antibody binding to immatu...
超分子
名称: High-concentration Fab Fragment of 2H2 antibody binding to immature Dengue virus at pH 7 タイプ: sample / ID: 1000 集合状態: Three Fab fragments bind to three pr on each trimeric spike Number unique components: 3