ジャーナル: Protein Cell / 年: 2022 タイトル: An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope. 著者: Zezhong Liu / Wei Xu / Zhenguo Chen / Wangjun Fu / Wuqiang Zhan / Yidan Gao / Jie Zhou / Yunjiao Zhou / Jianbo Wu / Qian Wang / Xiang Zhang / Aihua Hao / Wei Wu / Qianqian Zhang / Yaming Li / ...著者: Zezhong Liu / Wei Xu / Zhenguo Chen / Wangjun Fu / Wuqiang Zhan / Yidan Gao / Jie Zhou / Yunjiao Zhou / Jianbo Wu / Qian Wang / Xiang Zhang / Aihua Hao / Wei Wu / Qianqian Zhang / Yaming Li / Kaiyue Fan / Ruihong Chen / Qiaochu Jiang / Christian T Mayer / Till Schoofs / Youhua Xie / Shibo Jiang / Yumei Wen / Zhenghong Yuan / Kang Wang / Lu Lu / Lei Sun / Qiao Wang / 要旨: New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we ...New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
ダウンロード / ファイル: emd_31642.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
ボクセルのサイズ
X=Y=Z: 1.04 Å
密度
表面レベル
登録者による: 0.02
最小 - 最大
-0.07582625 - 0.118993744
平均 (標準偏差)
1.9392002e-05 (±0.0008550252)
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
400
400
400
Spacing
400
400
400
セル
A=B=C: 416.0 Å α=β=γ: 90.0 °
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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 : XG014 in complex with S trimer of SARS-CoV-2
全体
名称: XG014 in complex with S trimer of SARS-CoV-2
要素
複合体: XG014 in complex with S trimer of SARS-CoV-2
複合体: S trimer of SARS-CoV-2
複合体: XG014 Fab
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超分子 #1: XG014 in complex with S trimer of SARS-CoV-2
超分子
名称: XG014 in complex with S trimer of SARS-CoV-2 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 詳細: Fab fragment and S trimer generated by expression in 293 F cells
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)
組換発現
生物種: Homo sapiens (ヒト) / 組換細胞: 293F
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超分子 #2: S trimer of SARS-CoV-2
超分子
名称: S trimer of SARS-CoV-2 / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1