+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-39645 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | The structure of HKU1-B S protein with bsAb1 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | SARS-CoV-2 / Antibody / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
Authors | Xia LY / Zhang YY / Zhou Q | |||||||||
Funding support | China, 1 items
| |||||||||
Citation | Journal: Emerg Microbes Infect / Year: 2024 Title: A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2. Authors: Hancong Sun / Lingyun Xia / Jianhua Li / Yuanyuan Zhang / Guanying Zhang / Ping Huang / Xingxing Wang / Yue Cui / Ting Fang / Pengfei Fan / Qiang Zhou / Xiangyang Chi / Changming Yu / Abstract: SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which ...SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv) form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_39645.map.gz | 230.4 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-39645-v30.xml emd-39645.xml | 18.1 KB 18.1 KB | Display Display | EMDB header |
Images | emd_39645.png | 21.8 KB | ||
Filedesc metadata | emd-39645.cif.gz | 6.5 KB | ||
Others | emd_39645_half_map_1.map.gz emd_39645_half_map_2.map.gz | 226.3 MB 226.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-39645 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-39645 | HTTPS FTP |
-Validation report
Summary document | emd_39645_validation.pdf.gz | 888.4 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_39645_full_validation.pdf.gz | 887.9 KB | Display | |
Data in XML | emd_39645_validation.xml.gz | 16.1 KB | Display | |
Data in CIF | emd_39645_validation.cif.gz | 19.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-39645 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-39645 | HTTPS FTP |
-Related structure data
Related structure data | 8ywwMC 8ywxC 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_39645.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #1
File | emd_39645_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_39645_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : The structure of the bsAb1-Omicron BA.5 S complex
Entire | Name: The structure of the bsAb1-Omicron BA.5 S complex |
---|---|
Components |
|
-Supramolecule #1: The structure of the bsAb1-Omicron BA.5 S complex
Supramolecule | Name: The structure of the bsAb1-Omicron BA.5 S complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 134.104 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLIT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKHVD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLDVYYHKNN KSWMESEFRV Y SSANNCTF ...String: MFVFLVLLPL VSSQCVNLIT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKHVD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLDVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLGRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFDEVFNATR FASVYAWNRK RISNCVADYS VLYNFAPFFA FKCYGVSPTK LNDLCFTNVY ADSF VIRGN EVSQIAPGQT GNIADYNYKL PDDFTGCVIA WNSNKLDSKV GGNYNYRYRL FRKSNLKPFE RDISTEIYQA GNKPC NGVA GVNCYFPLQS YGFRPTYGVG HQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEYVNSSYEC DIPIGAGICA SYQTQTKSHG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLKRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKYFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGPALQIPFP MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STPSALGKLQ DVVNHNAQAL N TLVKQLSS KFGAISSVLN 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 YEQGS UniProtKB: Spike glycoprotein |
-Macromolecule #2: H4B6 heavy chain
Macromolecule | Name: H4B6 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.023781 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGD LVQPGGSLRL SCAASGFIVS RNYMSWVRQA PGKGLEWVSS IYSGGSTFYA GSVKGRFTIS RDNSKNTLYL QMNSLRAED TAIYYCARDI PRHGGDSWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN S GALTSGVH ...String: EVQLVESGGD LVQPGGSLRL SCAASGFIVS RNYMSWVRQA PGKGLEWVSS IYSGGSTFYA GSVKGRFTIS RDNSKNTLYL QMNSLRAED TAIYYCARDI PRHGGDSWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN S GALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKKVEPK |
-Macromolecule #3: H4B6 light chain
Macromolecule | Name: H4B6 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.399934 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: IRMTQSPASL SASIGDRVTI TCQASQDINK YLNWYQQKPG KAPRLLIYDA SNLETGVPSR FSGSGSGTDF TFTISSLQPE DIATYYCQQ YDNLPITFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String: IRMTQSPASL SASIGDRVTI TCQASQDINK YLNWYQQKPG KAPRLLIYDA SNLETGVPSR FSGSGSGTDF TFTISSLQPE DIATYYCQQ YDNLPITFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGE |
-Macromolecule #4: the scfv of H4D12
Macromolecule | Name: the scfv of H4D12 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 26.383195 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVQPGWSLRL SCVVSGLKFD DFAMHWVRQV PGKGLEWVSG LNWNGDNVAF ADSVKGRFTI SRDNAENSLY LQMNNLRPE DTAFYYCAKD SYYDILTGYS GAFDMWGQGT MVTVSSGGGG SGGGGSGGGG AIRMTQSPAT LSLSPGERAT L SCRASQSV ...String: EVQLVESGGG LVQPGWSLRL SCVVSGLKFD DFAMHWVRQV PGKGLEWVSG LNWNGDNVAF ADSVKGRFTI SRDNAENSLY LQMNNLRPE DTAFYYCAKD SYYDILTGYS GAFDMWGQGT MVTVSSGGGG SGGGGSGGGG AIRMTQSPAT LSLSPGERAT L SCRASQSV HNYLAWYQQK PGQAPRLLFY DASNRATGIP ARFSASASGT DSTLTISSLE PEDFAVYYCQ QRRNGYSFGQ GT KVEIK |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (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: 2.2 µm / Nominal defocus min: 1.2 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 368678 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |