Journal: Protein Cell / Year: 2022 Title: 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. Authors: 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 ...Authors: 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 / Abstract: 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.
History
Deposition
Aug 7, 2021
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Header (metadata) release
Oct 20, 2021
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Map release
Oct 20, 2021
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Update
Jul 6, 2022
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Current status
Jul 6, 2022
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
#259 - Jul 2021 Designed Proteins and Citizen Science similarity (1)
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Map
File
Download / File: emd_31639.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel size
X=Y=Z: 1.04 Å
Density
Contour Level
By AUTHOR: 0.01 / Movie #1: 0.01
Minimum - Maximum
-0.03441124 - 0.07105861
Average (Standard dev.)
6.661768e-06 (±0.0017931656)
Symmetry
Space group: 1
Details
EMDB XML:
Map geometry
Axis order
X
Y
Z
Origin
0
0
0
Dimensions
400
400
400
Spacing
400
400
400
Cell
A=B=C: 416.0 Å α=β=γ: 90.0 °
CCP4 map header:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.04
1.04
1.04
M x/y/z
400
400
400
origin x/y/z
0.000
0.000
0.000
length x/y/z
416.000
416.000
416.000
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
336
210
602
NX/NY/NZ
227
193
139
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
400
400
400
D min/max/mean
-0.034
0.071
0.000
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Supplemental data
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Sample components
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Entire : XG014 in complex with S trimer of SARS-CoV-2
Entire
Name: XG014 in complex with S trimer of SARS-CoV-2
Components
Complex: XG014 in complex with S trimer of SARS-CoV-2
Complex: S trimer of SARS-CoV-2
Protein or peptide: Spike glycoprotein
Complex: XG014
Protein or peptide: The light chain of XG014 Fab
Protein or peptide: The heavy chain of XG014
Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
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Supramolecule #1: XG014 in complex with S trimer of SARS-CoV-2
Supramolecule
Name: XG014 in complex with S trimer of SARS-CoV-2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 Details: Fab fragment and S trimer generated by expression in 293 F cells
Source (natural)
Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expression
Organism: Homo sapiens (human) / Recombinant cell: HEK293T
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Supramolecule #2: S trimer of SARS-CoV-2
Supramolecule
Name: S trimer of SARS-CoV-2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)
Organism: Homo sapiens (human)
Recombinant expression
Organism: Homo sapiens (human) / Recombinant cell: HEK293T
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