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Open data
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Basic information
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Title | Local resolution of BD55-5840 Fab and SARS-COV2 Omicron RBD | |||||||||
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Function / homology | ![]() Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / symbiont-mediated suppression of host innate immune response / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.26 Å | |||||||||
![]() | Zhang ZZ / Xiao JJ | |||||||||
Funding support | 1 items
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![]() | ![]() Title: BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Authors: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan ...Authors: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan Liu / Ran An / Xiaohua Hao / Yao Wang / Jing Wang / Rui Feng / Haiyan Sun / Lijuan Zhao / Wen Zhang / Dong Zhao / Jiang Zheng / Lingling Yu / Can Li / Na Zhang / Rui Wang / Xiao Niu / Sijie Yang / Xuetao Song / Yangyang Chai / Ye Hu / Yansong Shi / Linlin Zheng / Zhiqiang Li / Qingqing Gu / Fei Shao / Weijin Huang / Ronghua Jin / Zhongyang Shen / Youchun Wang / Xiangxi Wang / Junyu Xiao / Xiaoliang Sunney Xie / ![]() Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune- ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles, epitope distribution and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab and cilgavimab can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 168 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.2 KB 13.2 KB | Display Display | ![]() |
Images | ![]() | 27.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7wrzMC ![]() 7wr8C ![]() 7wrlC ![]() 7wroC ![]() 7x6aC ![]() 7xiwC ![]() 7xixC ![]() 7xiyC ![]() 7xizC ![]() 7xnqC ![]() 7xnrC ![]() 7xnsC M: atomic model generated by this map C: citing same article ( |
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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: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Local resolution of BD55-5840 Fab and SARS-COV2 Omicron RBD
Entire | Name: Local resolution of BD55-5840 Fab and SARS-COV2 Omicron RBD |
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Components |
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-Supramolecule #1: Local resolution of BD55-5840 Fab and SARS-COV2 Omicron RBD
Supramolecule | Name: Local resolution of BD55-5840 Fab and SARS-COV2 Omicron RBD type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: BD55-5840H
Macromolecule | Name: BD55-5840H / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.136394 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VQLAQSGSEL RKPGASVKVS CDTSGHSFTS NAIHWVRQAP GQGLEWMGWI NTDTGTPTYA QGFTGRFVFS LDTSARTAYL QISSLKADD TAVFYCARER DYSDYFFDYW GQGTLVTVSS |
-Macromolecule #2: BD55-5840L
Macromolecule | Name: BD55-5840L / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.635954 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVVMTQSPAS LSVSPGERAT LSCRARASLG ISTDLAWYQQ RPGQAPRLLI YGASTRATGI PARFSGSGSG TEFTLTISSL QSEDSAVYY CQQYSNWPLT FGGGTKVEIK |
-Macromolecule #3: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.983895 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: LCPFDEVFNA TRFASVYAWN RKRISNCVAD YSVLYNLAPF FTFKCYGVSP TKLNDLCFTN VYADSFVIRG DEVRQIAPGQ TGNIADYNY KLPDDFTGCV IAWNSNKLDS KVSGNYNYLY RLFRKSNLKP FERDISTEIY QAGNKPCNGV AGFNCYFPLR S YSFRPTYG ...String: LCPFDEVFNA TRFASVYAWN RKRISNCVAD YSVLYNLAPF FTFKCYGVSP TKLNDLCFTN VYADSFVIRG DEVRQIAPGQ TGNIADYNY KLPDDFTGCV IAWNSNKLDS KVSGNYNYLY RLFRKSNLKP FERDISTEIY QAGNKPCNGV AGFNCYFPLR S YSFRPTYG VGHQPYRVVV LSFELLHAPA TVCGK |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: OTHER |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.07 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.26 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 2765 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |