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Yorodumi- EMDB-40095: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40095 | |||||||||
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Title | 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer | |||||||||
Map data | ||||||||||
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 / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / 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 / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Kwon HJ / Zhang J / Kosikova M / Tang WC / Rodriguez UO / Peng HQ / Meseda CA / Pedro CL / Schmeisser F / Lu JM ...Kwon HJ / Zhang J / Kosikova M / Tang WC / Rodriguez UO / Peng HQ / Meseda CA / Pedro CL / Schmeisser F / Lu JM / Zhou B / Davis CT / Wentworth DE / Chen WH / Shriver MC / Pasetti MF / Weir JP / Chen B / Xie H | |||||||||
Funding support | United States, 1 items
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Citation | Journal: J Med Virol / Year: 2023 Title: Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2. Authors: Hyung J Kwon / Jun Zhang / Matina Kosikova / Weichun Tang / Uriel Ortega-Rodriguez / Hanqin Peng / Clement A Meseda / Cyntia L Pedro / Falko Schmeisser / Jianming Lu / Insung Kang / Bin Zhou ...Authors: Hyung J Kwon / Jun Zhang / Matina Kosikova / Weichun Tang / Uriel Ortega-Rodriguez / Hanqin Peng / Clement A Meseda / Cyntia L Pedro / Falko Schmeisser / Jianming Lu / Insung Kang / Bin Zhou / Charles T Davis / David E Wentworth / Wilbur H Chen / Mallory C Shriver / Robin S Barnes / Marcela F Pasetti / Jerry P Weir / Bing Chen / Hang Xie / Abstract: Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and ...Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC ) ≤135 ng/mL against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40095.map.gz | 362.8 MB | EMDB map data format | |
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Header (meta data) | emd-40095-v30.xml emd-40095.xml | 19.6 KB 19.6 KB | Display Display | EMDB header |
Images | emd_40095.png | 39.4 KB | ||
Others | emd_40095_half_map_1.map.gz emd_40095_half_map_2.map.gz | 384.9 MB 385.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40095 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40095 | HTTPS FTP |
-Related structure data
Related structure data | 8gjnMC 8gjmC 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_40095.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_40095_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_40095_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer
Entire | Name: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer |
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Components |
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-Supramolecule #1: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer
Supramolecule | Name: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3 Details: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 100 KDa |
-Macromolecule #1: Heavy chain of 17B10 Fab
Macromolecule | Name: Heavy chain of 17B10 Fab / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 15.353094 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGWSWIFLFL LSGTAGVLSE VQLQQSGPEL VKPGASVRIS CKTSGYTFTE YSMFWVKQSH GQSLEWIGGI NPNDDSTTYK QNFKGKATL TVDKSSSTAF MELRSLTSED SAVYYCTRDR YDGRVVDFWG QGTTLTVSS |
-Macromolecule #2: Light chain of 17B10 Fab
Macromolecule | Name: Light chain of 17B10 Fab / 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: 14.090899 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MRVPAHVFGF LLLWFPGTRC DIQMTQSPSS LSASLGERVS LICRASQEIS GYLSWLQQKP DGTIKRLIYA ASTLDSGVPK RFSGSRSGS EYSLTISSPE SEDFADYYCL QYASYPWTFG GGTKLEIK |
-Macromolecule #3: Spike protein S2'
Macromolecule | Name: Spike protein S2' / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22.218936 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TNLCPFGEVF NATRFASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGSTPCN GVEGFNCYFP L QSYGFQPT ...String: TNLCPFGEVF NATRFASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGSTPCN GVEGFNCYFP L QSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / 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
Concentration | 1 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 54.442 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 3124974 |
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Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final 3D classification | Software - Name: RELION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software: (Name: RELION, cryoSPARC) / Number images used: 439265 |
-Atomic model buiding 1
Initial model | Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Protocol: AB INITIO MODEL |
Output model | PDB-8gjn: |