[English] 日本語
Yorodumi- EMDB-28757: Structure of SARS-CoV-2 spike with antibody Fabs 2A10 and 1H2 (Lo... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28757 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of SARS-CoV-2 spike with antibody Fabs 2A10 and 1H2 (Local refinement of the RBD and Fabs 1H2 and 2A10) | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
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 / membrane fusion / 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: 3.18 Å | |||||||||
Authors | Yu X / Zyla D / Hastie KM / Saphire EO | |||||||||
Funding support | United States, 2 items
| |||||||||
Citation | Journal: Cell Rep / Year: 2023 Title: Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence. Authors: Kathryn M Hastie / Xiaoying Yu / Fernanda Ana-Sosa-Batiz / Dawid S Zyla / Stephanie S Harkins / Chitra Hariharan / Hal Wasserman / Michelle A Zandonatti / Robyn Miller / Erin Maule / Kenneth ...Authors: Kathryn M Hastie / Xiaoying Yu / Fernanda Ana-Sosa-Batiz / Dawid S Zyla / Stephanie S Harkins / Chitra Hariharan / Hal Wasserman / Michelle A Zandonatti / Robyn Miller / Erin Maule / Kenneth Kim / Kristen M Valentine / Sujan Shresta / Erica Ollmann Saphire / Abstract: Therapeutic antibodies are an important tool in the arsenal against coronavirus infection. However, most antibodies developed early in the pandemic have lost most or all efficacy against newly ...Therapeutic antibodies are an important tool in the arsenal against coronavirus infection. However, most antibodies developed early in the pandemic have lost most or all efficacy against newly emergent strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly those of the Omicron lineage. Here, we report the identification of a panel of vaccinee-derived antibodies that have broad-spectrum neutralization activity. Structural and biochemical characterization of the three broadest-spectrum antibodies reveal complementary footprints and differing requirements for avidity to overcome variant-associated mutations in their binding footprints. In the K18 mouse model of infection, these three antibodies exhibit protective efficacy against BA.1 and BA.2 infection. This study highlights the resilience and vulnerabilities of SARS-CoV-2 antibodies and provides road maps for further development of broad-spectrum therapeutics. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_28757.map.gz | 212 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-28757-v30.xml emd-28757.xml | 22 KB 22 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28757_fsc.xml | 15.8 KB | Display | FSC data file |
Images | emd_28757.png | 39 KB | ||
Masks | emd_28757_msk_1.map | 421.9 MB | Mask map | |
Others | emd_28757_half_map_1.map.gz emd_28757_half_map_2.map.gz | 390.9 MB 390.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28757 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28757 | HTTPS FTP |
-Validation report
Summary document | emd_28757_validation.pdf.gz | 876.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_28757_full_validation.pdf.gz | 876.4 KB | Display | |
Data in XML | emd_28757_validation.xml.gz | 24.9 KB | Display | |
Data in CIF | emd_28757_validation.cif.gz | 32.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28757 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28757 | HTTPS FTP |
-Related structure data
Related structure data | 8f0hMC 8e1gC 8f0gC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_28757.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_28757_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_28757_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_28757_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Structure of SARS-CoV-2 D614G spike in complex with antibody Fabs...
Entire | Name: Structure of SARS-CoV-2 D614G spike in complex with antibody Fabs 1H2 and 2A10 |
---|---|
Components |
|
-Supramolecule #1: Structure of SARS-CoV-2 D614G spike in complex with antibody Fabs...
Supramolecule | Name: Structure of SARS-CoV-2 D614G spike in complex with antibody Fabs 1H2 and 2A10 type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
---|
-Supramolecule #2: Antibody Fab 1H2 heavy chain, Antibody Fab 1H2 light chain, Antib...
Supramolecule | Name: Antibody Fab 1H2 heavy chain, Antibody Fab 1H2 light chain, Antibody Fab 2A10 heavy chain, Antibody Fab 2A10 light chain type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1, #3-#5 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: Spike glycoprotein
Supramolecule | Name: Spike glycoprotein / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #2 |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Macromolecule #1: Antibody Fab 1H2 heavy chain
Macromolecule | Name: Antibody Fab 1H2 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.783513 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLQQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ITWNSGTIGY ADSVKGRFTI SRDNAKNSLY LQMRSLRAE DTALYYCAKD SGRKLLWGRE DYYMGVWGKG TTVTV |
-Macromolecule #2: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 134.065656 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: MGVKVLFALI CIAVAEAQCV NLTTRTQLPP AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AIHVSGTNGT KRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLGVYY HKNNKSWMES E FRVYSSAN ...String: MGVKVLFALI CIAVAEAQCV NLTTRTQLPP AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AIHVSGTNGT KRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLGVYY HKNNKSWMES E FRVYSSAN NCTFEYVSQP FLMDLEGKQG NFKNLREFVF KNIDGYFKIY SKHTPINLVR DLPQGFSALE PLVDLPIGIN IT RFQTLLA LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTS NFRVQP TESIVRFPNI TNLCPFGEVF NATRFASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVY ADSFV IRGDEVRQIA PGQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAG STPC NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESN KKF LPFQQFGRDI ADTTDAVRDP QTLEILDITP CSFGGVSVIT PGTNTSNQVA VLYQDVNCTE VPVAIHADQL TPTWRVY ST GSNVFQTRAG CLIGAEHVNN SYECDIPIGA GICASYQTQT NSPGSASSVA SQSIIAYTMS LGAENSVAYS NNSIAIPT N FTISVTTEIL PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKD FGGFNFSQIL PDPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSG WTFGAGPALQ IPFPMQMAYR FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNQN A QALNTLVK QLSSNFGAIS SVLNDILSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQ SKRVDFC GKGYHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IIT TDNTFV SGNCDVVIGI VNNTVYDPLQ PELDSFKEEL DKYFKNHTSP DVDLGDISGI NASVVNIQKE IDRLNEVAKN LNES LIDLQ ELGKYEQ |
-Macromolecule #3: Antibody Fab 1H2 light chain
Macromolecule | Name: Antibody Fab 1H2 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 10.796722 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: SYELTQPPSV SVAPGKTARI TCGGSNIGSK SVHWYQQKPG QAPVLVIYYD SDRPSGIPER FSGSNSGNTA TLTISRVEAG DEADYYCQV WDSSSDHVVF GG |
-Macromolecule #4: Antibody Fab 2A10 heavy chain
Macromolecule | Name: Antibody Fab 2A10 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.750298 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLVESGGG LIQPGGSLRL SCAASEFIVS SNYMSWVRQA PGKGLEWVSL LYSGGTTYYA DSVKGRFTIS RDNSKNTLFL QMNSLRAED TAMYYCARDR GPWLHDYWGQ GTLVTV |
-Macromolecule #5: Antibody Fab 2A10 light chain
Macromolecule | Name: Antibody Fab 2A10 light chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.920188 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: DIVMTQSPSS LSASVGDRVT ITCQASQDIN KYCNWYQQKP GKAPKLLIYD ASNLETGVPS RFSGSGSGTD FTFTINSLQP EDIATYYCQ QYDNLPPTFG GGTKVEIKRT |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 / Details: TBS buffer pH 7.4 |
---|---|
Grid | Model: Quantifoil R2/2 / Material: COPPER / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / 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: 2.5 µm / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |