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Yorodumi- EMDB-23899: SARS-CoV-2 Spike RBD in complex with neutralizing Fab SARS2-38 (l... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23899 | |||||||||
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Title | SARS-CoV-2 Spike RBD in complex with neutralizing Fab SARS2-38 (local refinement) | |||||||||
Map data | Focused map of SARS2-38 antibody Fv bound to SARS-CoV-2 receptor binding domain | |||||||||
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 / 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: 3.16 Å | |||||||||
Authors | Adams LJ / Fremont DH / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||
Funding support | United States, 2 items
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Citation | Journal: bioRxiv / Year: 2021 Title: A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope. Authors: Laura VanBlargan / Lucas Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley Whitener / Lindsay ...Authors: Laura VanBlargan / Lucas Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley Whitener / Lindsay Droit / Ismael Aziati / Pei-Yong Shi / Adrian Creanga / Amarendra Pegu / Scott Handley / David Wang / Adrianus Boon / James E Crowe / Sean P J Whelan / Daved Fremont / Michael Diamond Abstract: With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of ...With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variants in vivo and lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23899.map.gz | 91.6 MB | EMDB map data format | |
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Header (meta data) | emd-23899-v30.xml emd-23899.xml | 15 KB 15 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23899_fsc.xml | 10.4 KB | Display | FSC data file |
Images | emd_23899.png | 55.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23899 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23899 | HTTPS FTP |
-Validation report
Summary document | emd_23899_validation.pdf.gz | 354.5 KB | Display | EMDB validaton report |
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Full document | emd_23899_full_validation.pdf.gz | 354.1 KB | Display | |
Data in XML | emd_23899_validation.xml.gz | 11.4 KB | Display | |
Data in CIF | emd_23899_validation.cif.gz | 15.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23899 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23899 | HTTPS FTP |
-Related structure data
Related structure data | 7mkmMC 7mklC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23899.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Focused map of SARS2-38 antibody Fv bound to SARS-CoV-2 receptor binding domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.16 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : SARS-CoV-2 spike bound by SARS2-38 antibody Fab
Entire | Name: SARS-CoV-2 spike bound by SARS2-38 antibody Fab |
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Components |
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-Supramolecule #1: SARS-CoV-2 spike bound by SARS2-38 antibody Fab
Supramolecule | Name: SARS-CoV-2 spike bound by SARS2-38 antibody Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-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: 21.247758 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 NGVGYQPYRV VVLSFELLHA |
-Macromolecule #2: SARS2-38 Fv heavy chain
Macromolecule | Name: SARS2-38 Fv heavy chain / 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: 12.490882 KDa |
Sequence | String: QVQLKESGPG LVAPSQSLSI TCTVSGFSLT RYGVHWVRQP PGKGLEWLGV IWADGSTYYN SALMSRLSIS KDNSKSQVFL NMNSLQTDD TAKYYCARDG RGYDDYWGQG TTLT |
-Macromolecule #3: SARS2-38 Fv light chain
Macromolecule | Name: SARS2-38 Fv light chain / 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: 11.419787 KDa |
Sequence | String: QIVLTQSPAI MSASPGEKVT MTCSASSTVS FIYWYQQKPG SSPRLLIYDT SNPASGVPVR FSGSGCGTSY YLTISRMEAE DAATYYCQQ WNTYPLTFGA GTKLEL |
-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
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |