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Yorodumi- EMDB-26879: Structure of the SARS-CoV-2 S 6P trimer in complex with the mouse... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26879 | |||||||||
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Title | Structure of the SARS-CoV-2 S 6P trimer in complex with the mouse antibody Fab fragment, M8a-6 | |||||||||
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 / 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 / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Fan C / Bjorkman PJ | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Immunity / Year: 2022 Title: Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes. Authors: Chengcheng Fan / Alexander A Cohen / Miso Park / Alfur Fu-Hsin Hung / Jennifer R Keeffe / Priyanthi N P Gnanapragasam / Yu E Lee / Han Gao / Leesa M Kakutani / Ziyan Wu / Harry Kleanthous / ...Authors: Chengcheng Fan / Alexander A Cohen / Miso Park / Alfur Fu-Hsin Hung / Jennifer R Keeffe / Priyanthi N P Gnanapragasam / Yu E Lee / Han Gao / Leesa M Kakutani / Ziyan Wu / Harry Kleanthous / Kathryn E Malecek / John C Williams / Pamela J Bjorkman / Abstract: Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding ...Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26879.map.gz | 168 MB | EMDB map data format | |
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Header (meta data) | emd-26879-v30.xml emd-26879.xml | 25.7 KB 25.7 KB | Display Display | EMDB header |
Images | emd_26879.png | 77.2 KB | ||
Others | emd_26879_additional_1.map.gz emd_26879_half_map_1.map.gz emd_26879_half_map_2.map.gz | 167.7 MB 165.3 MB 165.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26879 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26879 | HTTPS FTP |
-Validation report
Summary document | emd_26879_validation.pdf.gz | 1004.4 KB | Display | EMDB validaton report |
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Full document | emd_26879_full_validation.pdf.gz | 1003.9 KB | Display | |
Data in XML | emd_26879_validation.xml.gz | 14.8 KB | Display | |
Data in CIF | emd_26879_validation.cif.gz | 17.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26879 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26879 | HTTPS FTP |
-Related structure data
Related structure data | 7uz5MC 7uz4C 7uz6C 7uz7C 7uz8C 7uz9C 7uzaC 7uzbC 7uzcC 7uzdC 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_26879.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: local refinement map of RBD-Fab
File | emd_26879_additional_1.map | ||||||||||||
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Annotation | local refinement map of RBD-Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_26879_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_26879_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 S 6P in complex with M8a-6 Fab
Entire | Name: SARS-CoV-2 S 6P in complex with M8a-6 Fab |
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Components |
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-Supramolecule #1: SARS-CoV-2 S 6P in complex with M8a-6 Fab
Supramolecule | Name: SARS-CoV-2 S 6P in complex with M8a-6 Fab / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 25 KDa |
-Supramolecule #2: Severe acute respiratory syndrome coronavirus 2 spike glycoprotein
Supramolecule | Name: Severe acute respiratory syndrome coronavirus 2 spike glycoprotein type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1 / Details: stabilized with hexaproline |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: M8a-6 Fab VH and VL domains
Supramolecule | Name: M8a-6 Fab VH and VL domains / type: complex / ID: 3 / Chimera: Yes / Parent: 2 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #4: M8a-6 Fab CH1 and CL domains
Supramolecule | Name: M8a-6 Fab CH1 and CL domains / type: complex / ID: 4 / Chimera: Yes / Parent: 3 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-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: 139.344438 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 SYQTQTNSPA SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLN RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KDFGGFNFS QILPDPSKPS KRSPIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGP ALQIPFPMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTP SALGKLQDVV NQNAQALNTL V KQLSSNFG AISSVLNDIL SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FC GKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVS GNCDVV IGIVNNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQEL GKYEQ YIKWPSGRLV PRGSPGSGYI PEAPRDGQAY VRKDGEWVLL STFLGHHHHH H |
-Macromolecule #2: M8a-6 Fab heavy chain
Macromolecule | Name: M8a-6 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 25.353287 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQQPGTE LVMPGASVKL SCKTSGYTFT HYWMHWVKQR PGEGLEWIGE IAPSDNYVKY NQKFKGKSTL SVDRSSSTAY MQLSSLTSE DSAVYFCARP DNSGYPVYFD YWGQGTSLTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: QVQLQQPGTE LVMPGASVKL SCKTSGYTFT HYWMHWVKQR PGEGLEWIGE IAPSDNYVKY NQKFKGKSTL SVDRSSSTAY MQLSSLTSE DSAVYFCARP DNSGYPVYFD YWGQGTSLTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH HHHHH |
-Macromolecule #3: M8a-6 Fab light chain
Macromolecule | Name: M8a-6 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.52508 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSQKF MSTSLGDRVS ISCKASQDVG TTVAWYQQKP GQSPKLLIYW ASTRHTGVPD RFTGTGSGTD YTLTISSVAA EDLALYYCQ QHYNTPYTFG GGTKLEIERT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIVMTQSQKF MSTSLGDRVS ISCKASQDVG TTVAWYQQKP GQSPKLLIYW ASTRHTGVPD RFTGTGSGTD YTLTISSVAA EDLALYYCQ QHYNTPYTFG GGTKLEIERT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-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: 48 / 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 | 2 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 4293 / Average exposure time: 1.5 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 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 |