- EMDB-4713: Negative staining of antibodies cooperative complex formed by hum... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-4713
タイトル
Negative staining of antibodies cooperative complex formed by human fab7B10 and fab2C1 bound to the N. meningitidis antigen factor H binding protein (fHbp)
マップデータ
Negative staining of cooperative couple of human fab7B10 and fab2C1 bound to N.meningitidis antigen fHbp
試料
複合体: Ternary complex formed by fAb7B10, fAb2C1 and a molecule of fHbp
細胞器官・細胞要素: N.meningitidis antigen factor H binding protein (fHbp)
生物種
Homo sapiens (ヒト) / Neisseria meningitidis serogroup B (髄膜炎菌)
ジャーナル: Commun Biol / 年: 2019 タイトル: Structural basis for cooperativity of human monoclonal antibodies to meningococcal factor H-binding protein. 著者: Ilaria Peschiera / Maria Giuliani / Fabiola Giusti / Roberto Melero / Eugenio Paccagnini / Danilo Donnarumma / Werner Pansegrau / José M Carazo / Carlos O S Sorzano / Maria Scarselli / Vega ...著者: Ilaria Peschiera / Maria Giuliani / Fabiola Giusti / Roberto Melero / Eugenio Paccagnini / Danilo Donnarumma / Werner Pansegrau / José M Carazo / Carlos O S Sorzano / Maria Scarselli / Vega Masignani / Lassi J Liljeroos / Ilaria Ferlenghi / 要旨: Monoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated ...Monoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated among mAbs elicited by factor H-binding protein (fHbp), a surface-exposed lipoprotein and one of the key antigens included in both serogroup B meningococcus vaccine Bexsero and Trumenba. Here we report the structural and functional characterization of two cooperative mAbs pairs isolated from Bexsero vaccines. The 3D electron microscopy structures of the human mAb-fHbp-mAb cooperative complexes indicate that the angle formed between the antigen binding fragments (fAbs) assume regular angle and that fHbp is able to bind simultaneously and stably the cooperative mAbs pairs and human factor H (fH) in vitro. These findings shed light on molecular basis of the antibody-based mechanism of protection driven by simultaneous recognition of the different epitopes of the fHbp and underline that cooperativity is crucial in vaccine efficacy.
ダウンロード / ファイル: emd_4713.map.gz / 形式: CCP4 / 大きさ: 844.7 KB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Negative staining of cooperative couple of human fab7B10 and fab2C1 bound to N.meningitidis antigen fHbp
ボクセルのサイズ
X=Y=Z: 3.3 Å
密度
表面レベル
登録者による: 0.06 / ムービー #1: 0.06
最小 - 最大
-0.1403328 - 0.29140595
平均 (標準偏差)
-0.0002910064 (±0.01271074)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
-54
-54
-54
サイズ
60
60
60
Spacing
60
60
60
セル
A=B=C: 198.0 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
3.3
3.3
3.3
M x/y/z
60
60
60
origin x/y/z
0.000
0.000
0.000
length x/y/z
198.000
198.000
198.000
α/β/γ
90.000
90.000
90.000
MAP C/R/S
1
2
3
start NC/NR/NS
-54
-54
-54
NC/NR/NS
60
60
60
D min/max/mean
-0.140
0.291
-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 : Ternary complex formed by fAb7B10, fAb2C1 and a molecule of fHbp
全体
名称: Ternary complex formed by fAb7B10, fAb2C1 and a molecule of fHbp
要素
複合体: Ternary complex formed by fAb7B10, fAb2C1 and a molecule of fHbp
細胞器官・細胞要素: N.meningitidis antigen factor H binding protein (fHbp)
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超分子 #1: Ternary complex formed by fAb7B10, fAb2C1 and a molecule of fHbp
超分子
名称: Ternary complex formed by fAb7B10, fAb2C1 and a molecule of fHbp タイプ: complex / ID: 1 / 親要素: 0 詳細: The cooperative couple of fab was generated using the same CDR region of the cooperative couple of human IgG1 mAb7B10 and mAb2C1
由来(天然)
生物種: Homo sapiens (ヒト)
組換発現
生物種: Escherichia coli (大腸菌)
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超分子 #2: N.meningitidis antigen factor H binding protein (fHbp)
超分子
名称: N.meningitidis antigen factor H binding protein (fHbp) タイプ: organelle_or_cellular_component / ID: 2 / 親要素: 1 詳細: Is a surface-exposed lipoprotein expressed at different levels among the strains and it is present as recombinant antigen in both vaccines against meningococcal serogroup B licensed so far
由来(天然)
生物種: Neisseria meningitidis serogroup B (髄膜炎菌)
組換発現
生物種: Escherichia coli BL21(DE3) (大腸菌)
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実験情報
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構造解析
手法
ネガティブ染色法
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
染色
タイプ: NEGATIVE / 材質: 1% Uranyl acetate
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電子顕微鏡法
顕微鏡
FEI/PHILIPS CM200FEG
撮影
フィルム・検出器のモデル: TVIPS TEMCAM-F224 (2k x 2k) 平均電子線量: 30.0 e/Å2
電子線
加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN
電子光学系
照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD
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画像解析
最終 再構成
解像度のタイプ: BY AUTHOR / 解像度: 23.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 10000