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Yorodumi- EMDB-32517: SARS-CoV-2 Omicron variant spike in complex with three human neut... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32517 | |||||||||
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Title | SARS-CoV-2 Omicron variant spike in complex with three human neutralizing antibodies | |||||||||
Map data | SARS-CoV-2 Omicron variant spike in complex with three human neutralizing antibodies | |||||||||
Sample |
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Function / homology | Function and homology information 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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / immune response / 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 / extracellular space / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.82 Å | |||||||||
Authors | Zheng Q / Li S / Sun H / Zheng Z / Wang S | |||||||||
Funding support | 1 items
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Citation | Journal: Cell Rep / Year: 2022 Title: Three SARS-CoV-2 antibodies provide broad and synergistic neutralization against variants of concern, including Omicron. Authors: Siling Wang / Hui Sun / Yali Zhang / Lunzhi Yuan / Yizhen Wang / Tianying Zhang / Shaojuan Wang / Jinlei Zhang / Hai Yu / Hualong Xiong / Zimin Tang / Liqin Liu / Yang Huang / Xiuting Chen / ...Authors: Siling Wang / Hui Sun / Yali Zhang / Lunzhi Yuan / Yizhen Wang / Tianying Zhang / Shaojuan Wang / Jinlei Zhang / Hai Yu / Hualong Xiong / Zimin Tang / Liqin Liu / Yang Huang / Xiuting Chen / Tingting Li / Dong Ying / Chang Liu / Zihao Chen / Quan Yuan / Jun Zhang / Tong Cheng / Shaowei Li / Yi Guan / Qingbing Zheng / Zizheng Zheng / Ningshao Xia / Abstract: The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel ...The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: ∼20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32517.map.gz | 230.3 MB | EMDB map data format | |
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Header (meta data) | emd-32517-v30.xml emd-32517.xml | 17.1 KB 17.1 KB | Display Display | EMDB header |
Images | emd_32517.png | 66.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32517 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32517 | HTTPS FTP |
-Validation report
Summary document | emd_32517_validation.pdf.gz | 406.5 KB | Display | EMDB validaton report |
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Full document | emd_32517_full_validation.pdf.gz | 406.1 KB | Display | |
Data in XML | emd_32517_validation.xml.gz | 7.1 KB | Display | |
Data in CIF | emd_32517_validation.cif.gz | 8.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32517 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32517 | HTTPS FTP |
-Related structure data
Related structure data | 7wi0MC 7whzC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32517.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | SARS-CoV-2 Omicron variant spike in complex with three human neutralizing antibodies | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.778 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : SARS-CoV-2 Omicron variant spike in complex with three human neut...
Entire | Name: SARS-CoV-2 Omicron variant spike in complex with three human neutralizing antibodies |
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Components |
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-Supramolecule #1: SARS-CoV-2 Omicron variant spike in complex with three human neut...
Supramolecule | Name: SARS-CoV-2 Omicron variant spike in complex with three human neutralizing antibodies type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#7 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.167035 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TNLCPFDEVF NATRFASVYA WNRKRISNCV ADYSVLYNLA PFFTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKVSGNYNY LYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGFNCYFP L RSYSFRPT ...String: TNLCPFDEVF NATRFASVYA WNRKRISNCV ADYSVLYNLA PFFTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKVSGNYNY LYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGFNCYFP L RSYSFRPT YGVGHQPYRV VVLSFELLHA PATVCGP |
-Macromolecule #2: XMA04 heavy chain variable domain
Macromolecule | Name: XMA04 heavy chain variable domain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.517036 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG VVQPGRSLRL SCAASGFTFR TYAMHWVRQA PGKGLEWVAV MWNDGSNKYY ADSVKGRFTI SRDNSKNTLY LEMNSLRAE DTAVYYCARE GVAAAGSSSD AFDIWGQGTM VTVSS |
-Macromolecule #3: XMA01 heavy chain variable domain
Macromolecule | Name: XMA01 heavy chain variable domain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.198615 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVQPGGSLRL SCSASGFTFS SYAMHWVRQA PGKGLEYVSS ISSNGGSTYY ADSVKGRFTI SRDNSKNTLY LQMSSLRVE DAAVYYCVKH YQQQLLWGGP DVWGQGTTVT VSS |
-Macromolecule #4: IGL c4029_light_IGKV1-39_IGKJ2
Macromolecule | Name: IGL c4029_light_IGKV1-39_IGKJ2 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.616873 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPSS LSASVGDRVT ITCRASQSIS NFLNWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ QSYSTLYSFG QGTKLEIK |
-Macromolecule #5: IG c934_light_IGKV1-5_IGKJ1
Macromolecule | Name: IG c934_light_IGKV1-5_IGKJ1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.781073 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPVS LSASVGDRVT ITCRASQSIS TWLAWYQQKP GKAPKLLIYE TSSLESGVPS RFSGSGSGTE FTLTISSLQP DDFATYYCQ QFNSYPWTFG QGTKVEIK |
-Macromolecule #6: XMA09 heavy chain variable domain
Macromolecule | Name: XMA09 heavy chain variable domain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.272664 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SFAISWVRQA PGQGLEWMGG IIPIYGTANY AQKFQGRVTI TADESTSTAY MDLSSLRSE DTAVYYCARD GSSTYYPHNW FDPWGQGTLV TVSS |
-Macromolecule #7: IG c1437_light_IGLV1-40_IGLJ1
Macromolecule | Name: IG c1437_light_IGLV1-40_IGLJ1 / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.374391 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QSVLTQPPSV SGAPGQRVTI SCTGSSSNIG SGYDVHWYQQ LPGTAPKLLI YGNSNRPSGV PDRFSGSKSG TSASLAITGL QAEDEADYY CQSYDSSLSG VFGTGTKVTV L |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI F30 |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.82 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 123163 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |