ジャーナル: Science / 年: 2016 タイトル: Structural and molecular basis for Ebola virus neutralization by protective human antibodies. 著者: John Misasi / Morgan S A Gilman / Masaru Kanekiyo / Miao Gui / Alberto Cagigi / Sabue Mulangu / Davide Corti / Julie E Ledgerwood / Antonio Lanzavecchia / James Cunningham / Jean Jacques ...著者: John Misasi / Morgan S A Gilman / Masaru Kanekiyo / Miao Gui / Alberto Cagigi / Sabue Mulangu / Davide Corti / Julie E Ledgerwood / Antonio Lanzavecchia / James Cunningham / Jean Jacques Muyembe-Tamfun / Ulrich Baxa / Barney S Graham / Ye Xiang / Nancy J Sullivan / Jason S McLellan / 要旨: Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman ...Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.
#241 - 2020年1月 20年の分子を振り返って (Twenty Years of Molecules) 類似性 (4)
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マップ
ファイル
ダウンロード / ファイル: emd_3311.map.gz / 形式: CCP4 / 大きさ: 51.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Cryo-EM reconstruction of Ebola GP-Fab100-Fab114 ternary complex at pH 5
ボクセルのサイズ
X=Y=Z: 1.32 Å
密度
表面レベル
登録者による: 0.0213 / ムービー #1: 0.0213
最小 - 最大
-0.05702131 - 0.09657204
平均 (標準偏差)
0.00038889 (±0.00414544)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
240
240
240
Spacing
240
240
240
セル
A=B=C: 316.80002 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
1.32
1.32
1.32
M x/y/z
240
240
240
origin x/y/z
0.000
0.000
0.000
length x/y/z
316.800
316.800
316.800
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
-30
0
-64
NX/NY/NZ
61
61
129
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
240
240
240
D min/max/mean
-0.057
0.097
0.000
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添付データ
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試料の構成要素
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全体 : Ebola GP binds to Fab Fragments of mAb100 and mAb114
全体
名称: Ebola GP binds to Fab Fragments of mAb100 and mAb114
要素
試料: Ebola GP binds to Fab Fragments of mAb100 and mAb114
タンパク質・ペプチド: Ebola virus glycoprotein
タンパク質・ペプチド: mAb100
タンパク質・ペプチド: mAb114
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超分子 #1000: Ebola GP binds to Fab Fragments of mAb100 and mAb114
超分子
名称: Ebola GP binds to Fab Fragments of mAb100 and mAb114 タイプ: sample / ID: 1000 集合状態: One trimer of Ebola GP binds to three fab fragments of mAb100 and three fab fragments of mAb114 Number unique components: 3