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Yorodumi- EMDB-35741: Cryo-EM structure of SARS-CoV-2 spike protein in complex with dou... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35741 | |||||||||
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Title | Cryo-EM structure of SARS-CoV-2 spike protein in complex with double nAbs 8H12 and 1C4 (local refinement) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | SARS-CoV-2 / Neutralizing antibody / Cryo-EM / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / receptor-mediated endocytosis of virus by host cell / membrane fusion / 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 / 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 | Severe acute respiratory syndrome coronavirus 2 / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.77 Å | |||||||||
Authors | Sun H / Jiang Y / Zheng Q / Li S / Xia N | |||||||||
Funding support | 1 items
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Citation | Journal: Protein Cell / Year: 2024 Title: Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD. Authors: Hui Sun / Tingting Deng / Yali Zhang / Yanling Lin / Yanan Jiang / Yichao Jiang / Yang Huang / Shuo Song / Lingyan Cui / Tingting Li / Hualong Xiong / Miaolin Lan / Liqin Liu / Yu Li / ...Authors: Hui Sun / Tingting Deng / Yali Zhang / Yanling Lin / Yanan Jiang / Yichao Jiang / Yang Huang / Shuo Song / Lingyan Cui / Tingting Li / Hualong Xiong / Miaolin Lan / Liqin Liu / Yu Li / Qianjiao Fang / Kunyu Yu / Wenling Jiang / Lizhi Zhou / Yuqiong Que / Tianying Zhang / Quan Yuan / Tong Cheng / Zheng Zhang / Hai Yu / Jun Zhang / Wenxin Luo / Shaowei Li / Qingbing Zheng / Ying Gu / Ningshao Xia / Abstract: Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural ...Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35741.map.gz | 684.3 MB | EMDB map data format | |
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Header (meta data) | emd-35741-v30.xml emd-35741.xml | 19 KB 19 KB | Display Display | EMDB header |
Images | emd_35741.png | 35.8 KB | ||
Filedesc metadata | emd-35741.cif.gz | 6.1 KB | ||
Others | emd_35741_half_map_1.map.gz emd_35741_half_map_2.map.gz | 675.7 MB 675.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35741 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35741 | HTTPS FTP |
-Validation report
Summary document | emd_35741_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_35741_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_35741_validation.xml.gz | 20.5 KB | Display | |
Data in CIF | emd_35741_validation.cif.gz | 24.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35741 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35741 | HTTPS FTP |
-Related structure data
Related structure data | 8iv5MC 8iv4C 8iv8C 8ivaC 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_35741.map.gz / Format: CCP4 / Size: 729 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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
-Half map: #2
File | emd_35741_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35741_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of SARS-CoV-2 spike protein in complex with 8H12
Entire | Name: Cryo-EM structure of SARS-CoV-2 spike protein in complex with 8H12 |
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Components |
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-Supramolecule #1: Cryo-EM structure of SARS-CoV-2 spike protein in complex with 8H12
Supramolecule | Name: Cryo-EM structure of SARS-CoV-2 spike protein in complex with 8H12 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: SARS-CoV-2 spike protein
Supramolecule | Name: SARS-CoV-2 spike protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: nAbs 8H12,1C4
Supramolecule | Name: nAbs 8H12,1C4 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#5 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-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: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22.930721 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ESIVRFPNIT NLCPFGEVFN ATRFASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAP GQTGKIADYN YKLPDDFTGC VIAWNSNNLD SKVGGNYNYL YRLFRKSNLK PFERDISTEI YQAGSTPCNG V EGFNCYFP ...String: ESIVRFPNIT NLCPFGEVFN ATRFASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAP GQTGKIADYN YKLPDDFTGC VIAWNSNNLD SKVGGNYNYL YRLFRKSNLK PFERDISTEI YQAGSTPCNG V EGFNCYFP LQSYGFQPTN GVGYQPYRVV VLSFELLHAP ATVCGP UniProtKB: Spike glycoprotein |
-Macromolecule #2: light chain of 8H12
Macromolecule | Name: light chain of 8H12 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 11.945558 KDa |
Sequence | String: DIVMTQFQKF MSTSVGDRVS ITCKASQNVR TAVAWYQQKP GQSPKAMIYL ASNRHRGVPD RFTGSGCGTD FTLTISNVQC EDLADYFCL QHRNYPLTFG GGTKLEIK |
-Macromolecule #3: heavy chain of 8H12
Macromolecule | Name: heavy chain of 8H12 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 13.240784 KDa |
Sequence | String: EVKLEESGGG LVQPGGSMKL SCAASGFTFS DAWMDWVRQS PEKGLEWVAQ IRRKANNHAT YYAESVKGRF TISRDDSKSS VYLQMNSLR AEDTGIYYCI RGMTYAMDFW GQGTSVTVSS |
-Macromolecule #4: light chain of 1C4
Macromolecule | Name: light chain of 1C4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 11.642854 KDa |
Sequence | String: DIVLTQSPAT LSVTPGDNVS LSCRASQIIS NNLHWYQQKS HESPRLLIKY ASQSISGIPS RFSGSGSGTD FTLSINSVET EDFGMYFCQ QSNTWPLTCG SGTKLELN |
-Macromolecule #5: heavy chain of 1C4
Macromolecule | Name: heavy chain of 1C4 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 13.3849 KDa |
Sequence | String: QIQLVQSGPE LKKPGETVKI SCKASGYTFT DYGLNWVKQA PGKGLKWMGW INTYSGEPTY NDEFRGRFAF SLETSTITAY LKINNLKNE DTATYFCARG GNWDWYFDVW GAGTTVTVSS |
-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: 1.8 µm / Nominal defocus min: 0.9 µm |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.77 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 260028 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |