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- EMDB-26880: Structure of the SARS-CoV-2 S 6P trimer in complex with the mouse... -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Structure of the SARS-CoV-2 S 6P trimer in complex with the mouse antibody Fab fragment, M8a-28 | |||||||||
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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 / 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 / ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Fan C / Bjorkman PJ | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 167.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.6 KB 23.6 KB | Display Display | ![]() |
Images | ![]() | 76.5 KB | ||
Others | ![]() ![]() | 165.2 MB 165.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7uz6MC ![]() 7uz4C ![]() 7uz5C ![]() 7uz7C ![]() 7uz8C ![]() 7uz9C ![]() 7uzaC ![]() 7uzbC ![]() 7uzcC ![]() 7uzdC 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: 0.832 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_26880_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_26880_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : SARS-CoV-2 S 6P in complex with M8a-28 Fab
Entire | Name: SARS-CoV-2 S 6P in complex with M8a-28 Fab |
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Components |
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-Supramolecule #1: SARS-CoV-2 S 6P in complex with M8a-28 Fab
Supramolecule | Name: SARS-CoV-2 S 6P in complex with M8a-28 Fab / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() ![]() |
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: ![]() ![]() ![]() |
-Supramolecule #3: M8a-28 Fab VH and VL domains
Supramolecule | Name: M8a-28 Fab VH and VL domains / type: complex / ID: 3 / Chimera: Yes / Parent: 2 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() ![]() ![]() |
-Supramolecule #4: M8a-28 Fab CH1 and CL domains
Supramolecule | Name: M8a-28 Fab CH1 and CL domains / type: complex / ID: 4 / Chimera: Yes / Parent: 3 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() ![]() ![]() |
-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: ![]() ![]() ![]() |
Molecular weight | Theoretical: 139.344438 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 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-28 Fab heavy chain
Macromolecule | Name: M8a-28 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 25.443283 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLQQPGAE LVKPGASVKM SCKASGYNFN HYWISWVKQR PGQGLEWIGD IYPLSHFTTY NEKFTNRATL TVDTSSTTAY MQLNSLTSD DSAVFYCARW DYFDSRTFDY WGQGTTLTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: QVQLQQPGAE LVKPGASVKM SCKASGYNFN HYWISWVKQR PGQGLEWIGD IYPLSHFTTY NEKFTNRATL TVDTSSTTAY MQLNSLTSD DSAVFYCARW DYFDSRTFDY WGQGTTLTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKRV EPKSCDKTHH HHHH |
-Macromolecule #3: M8a-28 Fab light chain
Macromolecule | Name: M8a-28 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 23.490062 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DILLTQFPAI LSVSPGERVS FSCRASQTIG TNIHWYQQRI NGSPRLLIKY ASESISGIPS RFSGSGSGTD FSLSINNVES EDIADYYCQ QINSWPLTFG AGTKLDLKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DILLTQFPAI LSVSPGERVS FSCRASQTIG TNIHWYQQRI NGSPRLLIKY ASESISGIPS RFSGSGSGTD FSLSINNVES EDIADYYCQ QINSWPLTFG AGTKLDLKRT 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: 39 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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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 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 3375 / Average exposure time: 1.5 sec. / Average electron dose: 60.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Particle selection | Number selected: 964614 |
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Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2) |
Final 3D classification | Software - Name: cryoSPARC (ver. 3.2) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2) |
Final reconstruction | Applied symmetry - Point group: C3 (3 fold cyclic![]() |