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Open data
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Basic information
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Title | SARS-CoV-2 Spike (6P) in complex with 3 R1-32 Fabs and 3 ACE2 | |||||||||
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Function / homology | ![]() positive regulation of amino acid transport / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Liu B / Gao X / Li Z / Chen X / He J / Chen L / Xiong X | |||||||||
Funding support | ![]()
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![]() | ![]() Title: SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope. Authors: Ping He / Banghui Liu / Xijie Gao / Qihong Yan / Rongjuan Pei / Jing Sun / Qiuluan Chen / Ruitian Hou / Zimu Li / Yanjun Zhang / Jincun Zhao / Hao Sun / Bo Feng / Qian Wang / Haisu Yi / ...Authors: Ping He / Banghui Liu / Xijie Gao / Qihong Yan / Rongjuan Pei / Jing Sun / Qiuluan Chen / Ruitian Hou / Zimu Li / Yanjun Zhang / Jincun Zhao / Hao Sun / Bo Feng / Qian Wang / Haisu Yi / Peiyu Hu / Pingchao Li / Yudi Zhang / Zhilong Chen / Xuefeng Niu / Xiaolin Zhong / Liang Jin / Xiaofeng Liu / Kun Qu / Katarzyna A Ciazynska / Andrew P Carter / John A G Briggs / Jizheng Chen / Jinsong Liu / Xinwen Chen / Jun He / Ling Chen / Xiaoli Xiong / ![]() ![]() ![]() ![]() Abstract: Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1- ...Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 96.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23 KB 23 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.7 KB | Display | ![]() |
Images | ![]() | 137.6 KB | ||
Others | ![]() ![]() | 81 MB 81 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yegMC ![]() 7ydiC ![]() 7ydyC ![]() 7ye5C ![]() 7ye9C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.408 Å | ||||||||||||||||||||
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33772_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_33772_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : SARS-COV-2 Spike_GSAS_6P bound with three R1-32 Fabs and three ACE2
+Supramolecule #1: SARS-COV-2 Spike_GSAS_6P bound with three R1-32 Fabs and three ACE2
+Supramolecule #2: SARS-COV-2 Spike_GSAS_6P
+Supramolecule #3: ACE2
+Supramolecule #4: Fabs
+Macromolecule #1: Spike glycoprotein
+Macromolecule #2: Angiotensin-converting enzyme 2
+Macromolecule #3: heavy chain of R1-32 Fab
+Macromolecule #4: light chain of R1-32 Fab
+Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #7: ZINC ION
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 6989 / Average exposure time: 1.6 sec. / Average electron dose: 63.0 e/Å2 |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |