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Yorodumi- EMDB-33059: The SARS-CoV-2 receptor binding domain bound with the Fab fragmen... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33059 | |||||||||
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Title | The SARS-CoV-2 receptor binding domain bound with the Fab fragment of a human neutralizing antibody Ab354 | |||||||||
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / 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 | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Kamada K / Shirouzu M | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: iScience / Year: 2022 Title: Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models. Authors: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Tomomi Uchikubo-Kamo / Yuri Tomabechi / Kazuharu Hanada / Saya Moriyama / Yoshimasa ...Authors: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Tomomi Uchikubo-Kamo / Yuri Tomabechi / Kazuharu Hanada / Saya Moriyama / Yoshimasa Takahashi / Hirohito Ishigaki / Misako Nakayama / Cong Thanh Nguyen / Yoshinori Kitagawa / Yasushi Itoh / Masaki Imai / Tadashi Maemura / Yuri Furusawa / Hiroshi Ueki / Kiyoko Iwatsuki-Horimoto / Mutsumi Ito / Seiya Yamayoshi / Yoshihiro Kawaoka / Mikako Shirouzu / Makoto Ishii / Hideyuki Saya / Yasushi Kondo / Yuko Kaneko / Katsuya Suzuki / Koichi Fukunaga / Tsutomu Takeuchi / Abstract: The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In ...The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from patients with COVID-19-convalescent, and identified antibodies that exhibited the comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33059.map.gz | 11.4 MB | EMDB map data format | |
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Header (meta data) | emd-33059-v30.xml emd-33059.xml | 23.9 KB 23.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_33059_fsc.xml | 5.7 KB | Display | FSC data file |
Images | emd_33059.png | 80.7 KB | ||
Others | emd_33059_additional_1.map.gz emd_33059_half_map_1.map.gz emd_33059_half_map_2.map.gz | 14 MB 11.5 MB 11.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33059 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33059 | HTTPS FTP |
-Validation report
Summary document | emd_33059_validation.pdf.gz | 665.4 KB | Display | EMDB validaton report |
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Full document | emd_33059_full_validation.pdf.gz | 664.9 KB | Display | |
Data in XML | emd_33059_validation.xml.gz | 11.2 KB | Display | |
Data in CIF | emd_33059_validation.cif.gz | 15.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33059 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33059 | HTTPS FTP |
-Related structure data
Related structure data | 7x8wMC 7x8yC 7x8zC 7x90C 7x91C 7x92C 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_33059.map.gz / Format: CCP4 / Size: 15 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.829 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_33059_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33059_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33059_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : The SARS-CoV-2 spike protein bound with the Fab fragment of a hum...
Entire | Name: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab354 |
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Components |
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-Supramolecule #1: The SARS-CoV-2 spike protein bound with the Fab fragment of a hum...
Supramolecule | Name: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab354 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 560 KDa |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 Details: From aa1209, additional tags are added at the C-terminal, with Foldon sequence, TEV(tobacco etch virus) protease recognition and cleavage site, AviTag(peptide that allows for enzymatic ...Details: From aa1209, additional tags are added at the C-terminal, with Foldon sequence, TEV(tobacco etch virus) protease recognition and cleavage site, AviTag(peptide that allows for enzymatic biotinylation),and 6xHis affinity tag. Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 141.459453 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 FKCYGVSPTK 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 DILSRLDPPE 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 YEQAAAGSGY IPEAPRDGQA YVRKDGEWVL LSTFLGSSGR ENLYFQGGGG SGLNDIFEAQ KIEWHEGHHH HHH |
-Macromolecule #2: Ab354 heavy chain
Macromolecule | Name: Ab354 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: 28.685436 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDPKGSLSWR ILLFLSLAFE LSYGLEQVQL VQSGAEVKKP GASVTVSCKA SGFLFTGYYM HWVRQAPGQG LEWMGWINPN SGASNYTRK FQGRVTMTRD TSISATYMKL SRLTSDDTAV YYCARDLAFS MVRGALDYWG QGTLVTVSSA STKGPSVFPL A PSSKSTSG ...String: MDPKGSLSWR ILLFLSLAFE LSYGLEQVQL VQSGAEVKKP GASVTVSCKA SGFLFTGYYM HWVRQAPGQG LEWMGWINPN SGASNYTRK FQGRVTMTRD TSISATYMKL SRLTSDDTAV YYCARDLAFS MVRGALDYWG QGTLVTVSSA STKGPSVFPL A PSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NT KVDKKVE PKSCENLYFQ GHHHHHH |
-Macromolecule #3: Ab354 light chain
Macromolecule | Name: Ab354 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: 25.935793 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDPKGSLSWR ILLFLSLAFE LSYGLEQLVL TQPPSASGSP GQSVTISCTG TSSDVGGYNY VSWYQHHPGK APKLMIYEVS KRPSGVPDR FSGSKSGNTA SLTVSGLQAE DEADYYCNSY AGNNNWVFGT GTKVTVLGQP KANPTVTLFP PSSEELQANK A TLVCLISD ...String: MDPKGSLSWR ILLFLSLAFE LSYGLEQLVL TQPPSASGSP GQSVTISCTG TSSDVGGYNY VSWYQHHPGK APKLMIYEVS KRPSGVPDR FSGSKSGNTA SLTVSGLQAE DEADYYCNSY AGNNNWVFGT GTKVTVLGQP KANPTVTLFP PSSEELQANK A TLVCLISD FYPGAVTVAW KADSSPVKAG VETTTPSKQS NNKYAASSYL SLTPEQWKSH RSYSCQVTHE GSTVEKTVAP TE CS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.84 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R0.6/1 / Material: COPPER / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 100.0 K / Max: 100.0 K |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: COUNTING / 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 / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |