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- EMDB-33643: The SARS-CoV-2 receptor binding domain bound with the Fab fragmen... -
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Open data
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Basic information
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Title | The SARS-CoV-2 receptor binding domain bound with the Fab fragment of a human neutralizing antibody Ab816 | |||||||||
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![]() | severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike trimer / COVID-19 / human neutralizing antibody / RBD / VIRAL PROTEIN | |||||||||
Function / homology | ![]() 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
![]() | Uchikubo T / Shirouzu M | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents. Authors: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Qingshun Lin / Machie Sakuma / Eiki Kawahara / Isato Yamazaki / Tomomi Uchikubo-Kamo / ...Authors: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Qingshun Lin / Machie Sakuma / Eiki Kawahara / Isato Yamazaki / Tomomi Uchikubo-Kamo / Yuri Tomabechi / Kazuharu Hanada / Tamao Hisano / Saya Moriyama / Yoshimasa Takahashi / Mutsumi Ito / Masaki Imai / Tadashi Maemura / Yuri Furusawa / Seiya Yamayoshi / Yoshihiro Kawaoka / Mikako Shirouzu / Makoto Ishii / Hideyuki Saya / Yasushi Kondo / Yuko Kaneko / Katsuya Suzuki / Koichi Fukunaga / Tsutomu Takeuchi / / ![]() ![]() ![]() Abstract: Several antibody therapeutics have been developed against SARS-CoV-2; however, they have attenuated neutralizing ability against variants. In this study, we generated multiple broadly neutralizing ...Several antibody therapeutics have been developed against SARS-CoV-2; however, they have attenuated neutralizing ability against variants. In this study, we generated multiple broadly neutralizing antibodies from B cells of convalescents, by using two types of receptor-binding domains, Wuhan strain and the Gamma variant as bait. From 172 antibodies generated, six antibodies neutralized all strains prior to the Omicron variant, and the five antibodies were able to neutralize some of the Omicron sub-strains. Structural analysis showed that these antibodies have a variety of characteristic binding modes, such as ACE2 mimicry. We subjected a representative antibody to the hamster infection model after introduction of the N297A modification, and observed a dose-dependent reduction of the lung viral titer, even at a dose of 2 mg/kg. These results demonstrated that our antibodies have certain antiviral activity as therapeutics, and highlighted the importance of initial cell-screening strategy for the efficient development of therapeutic antibodies. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.3 KB 21.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 5.7 KB | Display | ![]() |
Images | ![]() | 80.3 KB | ||
Others | ![]() ![]() | 11.4 MB 11.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7y6lMC ![]() 7x93C ![]() 7x94C ![]() 7x95C ![]() 7x96C ![]() 7y6nC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
-Half map: #1
File | emd_33643_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33643_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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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 Ab816 |
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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 Ab816 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
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: ![]() ![]() |
Molecular weight | Theoretical: 141.459453 KDa |
Recombinant expression | Organism: ![]() |
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 UniProtKB: Spike glycoprotein |
-Macromolecule #2: Ab816 heavy chain
Macromolecule | Name: Ab816 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 28.789537 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDPKGSLSWR ILLFLSLAFE LSYGLEQVQL VQSGAEVKKP GESLMISCKA SGYNFRNYWI AWVRQMPGKG LEWMGIIHPG DSDIRYRPS LQGHVTISAD KSITTAYLQW GSLKASDTAM YYCTRITTDA DSSGLFHYWG QGTLVTVSSA STKGPSVFPL A PSSKSTSG ...String: MDPKGSLSWR ILLFLSLAFE LSYGLEQVQL VQSGAEVKKP GESLMISCKA SGYNFRNYWI AWVRQMPGKG LEWMGIIHPG DSDIRYRPS LQGHVTISAD KSITTAYLQW GSLKASDTAM YYCTRITTDA DSSGLFHYWG QGTLVTVSSA STKGPSVFPL A PSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NT KVDKKVE PKSCENLYFQ GHHHHHH |
-Macromolecule #3: Ab816 light chain
Macromolecule | Name: Ab816 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.293455 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDPKGSLSWR ILLFLSLAFE LSYGLEEIVL TQSPSTLSAS VGDRVTITCR ASQNIYTWLA WYQRKPGKAP KVLIYKASSL ESGVPSRFS GSGSGTEFTL TISSLQPDDF ATYYCQQYKS AWSFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC L LNNFYPRE ...String: MDPKGSLSWR ILLFLSLAFE LSYGLEEIVL TQSPSTLSAS VGDRVTITCR ASQNIYTWLA WYQRKPGKAP KVLIYKASSL ESGVPSRFS GSGSGTEFTL TISSLQPDDF ATYYCQQYKS AWSFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC L LNNFYPRE AKVQWKVDNA LQSGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE |
-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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.84 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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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: ![]() |
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 |