[English] 日本語
![](img/lk-miru.gif)
- EMDB-26882: Structure of the SARS-CoV-2 Omicron BA.1 S 6P trimer in complex w... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of the SARS-CoV-2 Omicron BA.1 S 6P trimer in complex with the mouse antibody Fab fragment, M8a-31 | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
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 / symbiont-mediated suppression of host innate immune response / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / 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: 3.1 Å | |||||||||
![]() | Fan C / Bjorkman PJ | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 168 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 25.6 KB 25.6 KB | Display Display | ![]() |
Images | ![]() | 77.8 KB | ||
Others | ![]() ![]() ![]() | 167.6 MB 165.1 MB 165.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7uz8MC ![]() 7uz4C ![]() 7uz5C ![]() 7uz6C ![]() 7uz7C ![]() 7uz9C ![]() 7uzaC ![]() 7uzbC ![]() 7uzcC ![]() 7uzdC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Additional map: #1
File | emd_26882_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_26882_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_26882_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : SARS-CoV-2 Omicron BA.1 S 6P in complex with M8a-31 Fab
Entire | Name: SARS-CoV-2 Omicron BA.1 S 6P in complex with M8a-31 Fab |
---|---|
Components |
|
-Supramolecule #1: SARS-CoV-2 Omicron BA.1 S 6P in complex with M8a-31 Fab
Supramolecule | Name: SARS-CoV-2 Omicron BA.1 S 6P in complex with M8a-31 Fab type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3 / Details: stabilized with hexaproline |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25 KDa |
-Supramolecule #2: Severe acute respiratory syndrome coronavirus 2 Omicron spike gly...
Supramolecule | Name: Severe acute respiratory syndrome coronavirus 2 Omicron spike glycoprotein type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: M8a-31 Fab VH and VL domains
Supramolecule | Name: M8a-31 Fab VH and VL domains / type: complex / ID: 3 / Chimera: Yes / Parent: 2 / Macromolecule list: #2-#3 |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Supramolecule #4: M8a-31 Fab CH1 and CL domains
Supramolecule | Name: M8a-31 Fab CH1 and CL domains / type: complex / ID: 4 / Chimera: Yes / Parent: 3 / Macromolecule list: #2-#3 |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 139.503156 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIVR EPEDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFD EVFNATRFAS VYAWNRKRIS NCVADYSVLY NLAPFFTFKC YGVSPTKLND LCFTNVYADS FVIR GDEVR QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKVSGN YNYLYRLFRK SNLKPFERDI STEIYQAGNK PCNGV AGFN CYFPLRSYSF RPTYGVGHQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLK GTGVLTESNK KFLPFQ QFG RDIADTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEY VNNSYECDIP IGAGICASYQ TQTKSHASVA SQSIIAYTMS LGAENSVAYS NNSIAIPTNF TISVTTEI L PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLKRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKYF GGFNFSQIL PDPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFK GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGPALQ IPFPMQMAYR FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNHN AQALNTLVKQ L SSKFGAIS SVLNDIFSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQSKRVDFCG KG YHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNC DVVIGI VNNTVYDPLQ PELDSFKEEL DKYFKNHTSP DVDLGDISGI NASVVNIQKE IDRLNEVAKN LNESLIDLQE LGKY EQYIK WPSGRLVPRG SPGSGYIPEA PRDGQAYVRK DGEWVLLSTF LGHHHHHH |
-Macromolecule #2: M8a-31 Fab heavy chain
Macromolecule | Name: M8a-31 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.474289 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLKQSVAE LVRPGASVKV SCTASGFNIK NIYMHWVKQR PEQGLDWIGR IDPANGNSRY APKFQDKATI TADTSSNTAY LQLSSLTSE DTAIYYCADE GWGFANWGQG TLVTVSAAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS G ALTSGVHT ...String: EVQLKQSVAE LVRPGASVKV SCTASGFNIK NIYMHWVKQR PEQGLDWIGR IDPANGNSRY APKFQDKATI TADTSSNTAY LQLSSLTSE DTAIYYCADE GWGFANWGQG TLVTVSAAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS G ALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKRVEPKS CDKTHHHHHH |
-Macromolecule #3: M8a-31 Fab light chain
Macromolecule | Name: M8a-31 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.188906 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIVMTQSPSS LTVTAGEKVT MSCKSSQSLL NSGNQKNYLT WYQQKVGQPP KLLIYWASTR DPGVPDRFTG SGFGTDFTLT ISSVQAEDL AVYYCQNDYS YPLTFGAGTK VELKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA L QSGNSQES ...String: DIVMTQSPSS LTVTAGEKVT MSCKSSQSLL NSGNQKNYLT WYQQKVGQPP KLLIYWASTR DPGVPDRFTG SGFGTDFTLT ISSVQAEDL AVYYCQNDYS YPLTFGAGTK VELKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA L QSGNSQES VTEQDSKDST YSLSSTLTLS KADYEKHKVY ACEVTHQGLS SPVTKSFNRG EC |
-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: 27 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 2 mg/mL | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 8 Component:
| ||||||||||||
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 |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 5786 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
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 |