+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25574 | |||||||||
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Title | SARS-CoV-2 S-RBD + Fab 54042-4 | |||||||||
Map data | Local refinement. SARS-CoV-2 S RBD bound to 54042-4 Fab | |||||||||
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 / symbiont-mediated suppression of host innate immune response / structural constituent of virion ...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 / symbiont-mediated suppression of host innate immune response / 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 / 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: 2.69 Å | |||||||||
Authors | Johnson NV / Mclellan JS | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Rep / Year: 2021 Title: Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition. Authors: Kevin J Kramer / Nicole V Johnson / Andrea R Shiakolas / Naveenchandra Suryadevara / Sivakumar Periasamy / Nagarajan Raju / Jazmean K Williams / Daniel Wrapp / Seth J Zost / Lauren M Walker ...Authors: Kevin J Kramer / Nicole V Johnson / Andrea R Shiakolas / Naveenchandra Suryadevara / Sivakumar Periasamy / Nagarajan Raju / Jazmean K Williams / Daniel Wrapp / Seth J Zost / Lauren M Walker / Steven C Wall / Clinton M Holt / Ching-Lin Hsieh / Rachel E Sutton / Ariana Paulo / Rachel S Nargi / Edgar Davidson / Benjamin J Doranz / James E Crowe / Alexander Bukreyev / Robert H Carnahan / Jason S McLellan / Ivelin S Georgiev / Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable ...The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25574.map.gz | 316.9 MB | EMDB map data format | |
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Header (meta data) | emd-25574-v30.xml emd-25574.xml | 20.2 KB 20.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25574_fsc.xml | 18.4 KB | Display | FSC data file |
Images | emd_25574.png | 65.8 KB | ||
Others | emd_25574_additional_1.map.gz emd_25574_half_map_1.map.gz emd_25574_half_map_2.map.gz | 425.7 MB 475.4 MB 483.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25574 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25574 | HTTPS FTP |
-Validation report
Summary document | emd_25574_validation.pdf.gz | 593.4 KB | Display | EMDB validaton report |
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Full document | emd_25574_full_validation.pdf.gz | 592.9 KB | Display | |
Data in XML | emd_25574_validation.xml.gz | 26.5 KB | Display | |
Data in CIF | emd_25574_validation.cif.gz | 34.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25574 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25574 | HTTPS FTP |
-Related structure data
Related structure data | 7t01MC 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_25574.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Local refinement. SARS-CoV-2 S RBD bound to 54042-4 Fab | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.81 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Full SARS-CoV-2 spike trimer with 3 copies of 54042-4 bound
File | emd_25574_additional_1.map | ||||||||||||
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Annotation | Full SARS-CoV-2 spike trimer with 3 copies of 54042-4 bound | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map
File | emd_25574_half_map_1.map | ||||||||||||
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Annotation | Half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map
File | emd_25574_half_map_2.map | ||||||||||||
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Annotation | Half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of SARS-CoV-2 S-ECD with 54042-4 Fab
Entire | Name: Complex of SARS-CoV-2 S-ECD with 54042-4 Fab |
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Components |
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-Supramolecule #1: Complex of SARS-CoV-2 S-ECD with 54042-4 Fab
Supramolecule | Name: Complex of SARS-CoV-2 S-ECD with 54042-4 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 22.603408 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: FPNITNLCPF GEVFNATRFA SVYAWNRKRI SNCVADYSVL YNSASFSTFK CYGVSPTKLN DLCFTNVYAD SFVIRGDEVR QIAPGQTGK IADYNYKLPD DFTGCVIAWN SNNLDSKVGG NYNYLYRLFR KSNLKPFERD ISTEIYQAGS TPCNGVEGFN C YFPLQSYG ...String: FPNITNLCPF GEVFNATRFA SVYAWNRKRI SNCVADYSVL YNSASFSTFK CYGVSPTKLN DLCFTNVYAD SFVIRGDEVR QIAPGQTGK IADYNYKLPD DFTGCVIAWN SNNLDSKVGG NYNYLYRLFR KSNLKPFERD ISTEIYQAGS TPCNGVEGFN C YFPLQSYG FQPTNGVGYQ PYRVVVLSFE LLHAPATVCG PKK |
-Macromolecule #2: 54042-4 Fab - Heavy Chain
Macromolecule | Name: 54042-4 Fab - Heavy Chain / 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: 13.145856 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QITLKESGPT LVKPTQTLTL TCTFSGFSLS TIGVGVSWIR QPPGKALDWL ALIYWDDDKR YSPSLKSRLT VTMDTSKNQV VLTLTNMDP VDTATYFCAH GLFSSSDWGG LDVWGQGTTV T |
-Macromolecule #3: 54042-4 Fab - Light Chain
Macromolecule | Name: 54042-4 Fab - Light Chain / 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: 11.734157 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DMQMTQSPSS LSASVGDRVT ITCRASQSVF TYLNWYQQKP GKAPKLLIYA ASRLQSGVPS RFRGSGSGTD FTLTISSLQP EDFATYYCQ QSHSTPFIFG PGTKVDIK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.5 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV / Details: -4 force, 3 s blot. | |||||||||
Details | Sample was monodisperse. All S proteins had 3 Fabs bound. |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.0 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: 0.0025 µm / Nominal defocus min: 0.0015 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |