+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17819 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | XBB 1.0 RBD bound to P4J15 (Local) | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | SARS-Cov2 / CryoEM / RBD-binding / FAB / VIRAL PROTEIN | |||||||||
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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.85 Å | |||||||||
Authors | Duhoo Y / Lau K | |||||||||
Funding support | Switzerland, 1 items
| |||||||||
Citation | Journal: J Infect / Year: 2023 Title: Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys. Authors: Craig Fenwick / Priscilla Turelli / Yoan Duhoo / Kelvin Lau / Cécile Herate / Romain Marlin / Myriam Lamrayah / Jérémy Campos / Line Esteves-Leuenberger / Alex Farina / Charlène Raclot / ...Authors: Craig Fenwick / Priscilla Turelli / Yoan Duhoo / Kelvin Lau / Cécile Herate / Romain Marlin / Myriam Lamrayah / Jérémy Campos / Line Esteves-Leuenberger / Alex Farina / Charlène Raclot / Vanessa Genet / Flurin Fiscalini / Julien Cesborn / Laurent Perez / Nathalie Dereuddre-Bosquet / Vanessa Contreras / Kyllian Lheureux / Francis Relouzat / Rana Abdelnabi / Pieter Leyssen / Yves Lévy / Florence Pojer / Roger Le Grand / Didier Trono / Giuseppe Pantaleo / Abstract: OBJECTIVES: Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic ...OBJECTIVES: Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. METHODS: Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 ...METHODS: Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. RESULTS: The P4J15 mAb shows <20 ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. CONCLUSIONS: The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_17819.map.gz | 168.2 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-17819-v30.xml emd-17819.xml | 23.5 KB 23.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_17819_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_17819.png | 29.7 KB | ||
Masks | emd_17819_msk_1.map | 178 MB | Mask map | |
Filedesc metadata | emd-17819.cif.gz | 6.9 KB | ||
Others | emd_17819_additional_1.map.gz emd_17819_half_map_1.map.gz emd_17819_half_map_2.map.gz | 305 MB 164.9 MB 164.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-17819 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17819 | HTTPS FTP |
-Related structure data
Related structure data | 8pq2MC 8psdC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_17819.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.2681 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_17819_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: Enhanced map using EMready.
File | emd_17819_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Enhanced map using EMready. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_17819_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_17819_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Spike XBB.1 RBD up - P4J15 Fab (local)
Entire | Name: Spike XBB.1 RBD up - P4J15 Fab (local) |
---|---|
Components |
|
-Supramolecule #1: Spike XBB.1 RBD up - P4J15 Fab (local)
Supramolecule | Name: Spike XBB.1 RBD up - P4J15 Fab (local) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 Details: local refinement from the Full XBB.1 spike and RBD complex. |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 72 kDa/nm |
-Macromolecule #1: P4J15 Fragment Antigen-Binding Heavy Chain
Macromolecule | Name: P4J15 Fragment Antigen-Binding Heavy Chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.375937 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQIQQWGAG LLKPSETLSL TCAVYDESFS DYFWTWIRQS PGMGLEWIGE VTHTGSANYN PSLMSRVTMS RDTSKNQISL KLTSVTAAD TAVYYCARDS PLGSIIKRGD YWGQGTLVTV SS |
-Macromolecule #2: P4J15 Fragment Antigen-Binding Light Chain
Macromolecule | Name: P4J15 Fragment Antigen-Binding Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.76199 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: DIQMTQSPSS LSASVGDRVT VTCQASQGIT NYVNWYQQKP GKAPKLLIYH ASHLETGVPS RFSGSGSGTD FTFTISSLQP EDFATYYCQ QFDHLPPTFG QGTRLEIK |
-Macromolecule #3: Spike protein S2'
Macromolecule | Name: Spike protein S2' / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 21.900672 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: TNLCPFHEVF NATTFASVYA WNRKRISNCV ADYSVIYNFA PFFAFKCYGV SPTKLNDLCF TNVYADSFVI RGNEVSQIAP GQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKPSGNYNY LYRLFRKSKL KPFERDISTE IYQAGNKPCN GVAGSNCYSP L QSYGFRPT ...String: TNLCPFHEVF NATTFASVYA WNRKRISNCV ADYSVIYNFA PFFAFKCYGV SPTKLNDLCF TNVYADSFVI RGNEVSQIAP GQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKPSGNYNY LYRLFRKSKL KPFERDISTE IYQAGNKPCN GVAGSNCYSP L QSYGFRPT YGVGHQPYRV VVLSFELLHA PATVCGP UniProtKB: Spike glycoprotein |
-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 |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7.4 Component:
| |||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 10 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 90 sec. / Pretreatment - Atmosphere: AIR | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 96000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.6 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
---|---|
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
Output model | PDB-8pq2: |