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Yorodumi- EMDB-24878: J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut2 S... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24878 | |||||||||
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Title | J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut2 S protein (conformation 2) | |||||||||
Map data | Sharpened map | |||||||||
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 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Ozorowski G / Torres JL / Ward AB | |||||||||
Funding support | Italy, 2 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody. Authors: Jonathan L Torres / Gabriel Ozorowski / Emanuele Andreano / Hejun Liu / Jeffrey Copps / Giulia Piccini / Lorena Donnici / Matteo Conti / Cyril Planchais / Delphine Planas / Noemi Manganaro / ...Authors: Jonathan L Torres / Gabriel Ozorowski / Emanuele Andreano / Hejun Liu / Jeffrey Copps / Giulia Piccini / Lorena Donnici / Matteo Conti / Cyril Planchais / Delphine Planas / Noemi Manganaro / Elisa Pantano / Ida Paciello / Piero Pileri / Timothée Bruel / Emanuele Montomoli / Hugo Mouquet / Olivier Schwartz / Claudia Sala / Raffaele De Francesco / Ian A Wilson / Rino Rappuoli / Andrew B Ward / Abstract: As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome ...As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryoelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_24878.map.gz | 204.3 MB | EMDB map data format | |
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Header (meta data) | emd-24878-v30.xml emd-24878.xml | 22.5 KB 22.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_24878_fsc.xml | 13.3 KB | Display | FSC data file |
Images | emd_24878.png | 84.1 KB | ||
Masks | emd_24878_msk_1.map | 216 MB | Mask map | |
Others | emd_24878_half_map_1.map.gz emd_24878_half_map_2.map.gz | 200.8 MB 200.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24878 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24878 | HTTPS FTP |
-Validation report
Summary document | emd_24878_validation.pdf.gz | 820.5 KB | Display | EMDB validaton report |
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Full document | emd_24878_full_validation.pdf.gz | 820.1 KB | Display | |
Data in XML | emd_24878_validation.xml.gz | 21.5 KB | Display | |
Data in CIF | emd_24878_validation.cif.gz | 28 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24878 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24878 | HTTPS FTP |
-Related structure data
Related structure data | 7s6kMC 7s6iC 7s6jC 7s6lC 7sbuC 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_24878.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_24878_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_24878_half_map_1.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_24878_half_map_2.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : J08 fragment antigen binding in complex with SARS-2-CoV-6P-Mut2 S...
Entire | Name: J08 fragment antigen binding in complex with SARS-2-CoV-6P-Mut2 S protein |
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Components |
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-Supramolecule #1: J08 fragment antigen binding in complex with SARS-2-CoV-6P-Mut2 S...
Supramolecule | Name: J08 fragment antigen binding in complex with SARS-2-CoV-6P-Mut2 S protein type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 690 KDa |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 141.326422 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLVRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVCPTK LNDLCFTNVY ADSF VIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA GSTPC NGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ DVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEHVNNSYEC DIPIGAGICA SYQTQTNSPG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGPALQIPFP MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STPSALGKLQ DVVNQNAQAL N TLVKQLSS NFGAISSVLN DILSRLCPPE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK RV DFCGKGY HLMSFPQSAP HGVVFLHVTY VPAQEKNFTT APAICHDGKA HFPREGVFVS NGTHWFVTQR NFYEPQIITT DNT FVSGNC DVVIGIVNNT VYDPLQPELD SFKEELDKYF KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDL QELGK YEQGSGYIPE APRDGQAYVR KDGEWVLLST FLGRSLEVLF QGPGSAWSHP QFEKGGGSGG GGSGGSAWSH PQFEK |
-Macromolecule #2: J08 fragment antigen binding heavy chain variable domain
Macromolecule | Name: J08 fragment antigen binding heavy chain variable domain type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.961632 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYTISWVRQA PGQGLEWMGR IIPILDRVMY AQKFQGRVTI TADKSTSTAY MELSSLRSE DTAVYYCARR AIDSDTYVEQ SHFDYWGQGT LVTVSSAS |
-Macromolecule #3: J08 fragment antigen binding light chain variable domain
Macromolecule | Name: J08 fragment antigen binding light chain variable domain type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.252522 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVMTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPSLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QPLTFGGGTK VEIKRT |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 21 / 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 | 3 mg/mL | ||||||||||
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Buffer | pH: 8 Component:
Details: Detergent added shortly before freezing | ||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING | ||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: 3 s blot time. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 12.0 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.2 µm / Nominal magnification: 36000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-7s6k: |