[English] 日本語
Yorodumi- EMDB-33151: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex wi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33151 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab | |||||||||
Map data | Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab | |||||||||
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 / 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 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.08 Å | |||||||||
Authors | Liu Z / Liu S / Yuanzhu G | |||||||||
Funding support | China, 1 items
| |||||||||
Citation | Journal: Cell Discov / Year: 2023 Title: Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5. Authors: Yanqun Wang / An Yan / Deyong Song / Chuangchuang Dong / Muding Rao / Yuanzhu Gao / Ruxi Qi / Xiaomin Ma / Qiaoping Wang / Hongguang Xu / Hong Liu / Jing Han / Maoqin Duan / Shuo Liu / ...Authors: Yanqun Wang / An Yan / Deyong Song / Chuangchuang Dong / Muding Rao / Yuanzhu Gao / Ruxi Qi / Xiaomin Ma / Qiaoping Wang / Hongguang Xu / Hong Liu / Jing Han / Maoqin Duan / Shuo Liu / Xiaoping Yu / Mengqi Zong / Jianxia Feng / Jie Jiao / Huimin Zhang / Min Li / Beibei Yu / Yanxia Wang / Fanhao Meng / Xiaodan Ni / Ying Li / Zhenduo Shen / Baiping Sun / Xin Shao / Haifeng Zhao / Yanyan Zhao / Rui Li / Yanan Zhang / Guangying Du / Jun Lu / Chunna You / Hua Jiang / Lu Zhang / Lan Wang / Changlin Dou / Zheng Liu / Jincun Zhao / Abstract: SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, ...SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1-BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_33151.map.gz | 483.5 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-33151-v30.xml emd-33151.xml | 22.2 KB 22.2 KB | Display Display | EMDB header |
Images | emd_33151.png | 131.3 KB | ||
Others | emd_33151_half_map_1.map.gz emd_33151_half_map_2.map.gz | 475.8 MB 475.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33151 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33151 | HTTPS FTP |
-Validation report
Summary document | emd_33151_validation.pdf.gz | 853.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_33151_full_validation.pdf.gz | 852.7 KB | Display | |
Data in XML | emd_33151_validation.xml.gz | 18.8 KB | Display | |
Data in CIF | emd_33151_validation.cif.gz | 22.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33151 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33151 | HTTPS FTP |
-Related structure data
Related structure data | 7xdlMC 7xczC 7xdaC 7xdbC 7xdkC 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_33151.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.66 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in...
File | emd_33151_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in...
File | emd_33151_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex wi...
Entire | Name: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab |
---|---|
Components |
|
-Supramolecule #1: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex wi...
Supramolecule | Name: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#5 |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #2: SARS-CoV-2 Delta Spike protein
Supramolecule | Name: SARS-CoV-2 Delta Spike protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: BA7208 and BA7125 fab
Supramolecule | Name: BA7208 and BA7125 fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#5 |
---|
-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: 123.251586 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: PAYTNSFTRG VYYPDKVFRS SVLHSTQDLF LPFFSNVTWF HAIHVSGTNG TKRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKT QSLLIVNNAT NVVIKVCEFQ FCNDPFLGVY YHKNNKSWME SGVYSSANNC TFEYVSQPFL MDLEGKQGNF K NLREFVFK ...String: PAYTNSFTRG VYYPDKVFRS SVLHSTQDLF LPFFSNVTWF HAIHVSGTNG TKRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKT QSLLIVNNAT NVVIKVCEFQ FCNDPFLGVY YHKNNKSWME SGVYSSANNC TFEYVSQPFL MDLEGKQGNF K NLREFVFK NIDGYFKIYS KHTPINLVRD LPQGFSALEP LVDLPIGINI TRFQTLLALH RSYLTPGDSS SGWTAGAAAY YV GYLQPRT FLLKYNENGT ITDAVDCALD PLSETKCTLK SFTVEKGIYQ TSNFRVQPTE SIVRFPNITN LCPFGEVFNA TRF ASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGKIADYNY KLPD DFTGC VIAWNSNNLD SKVGGNYNYR YRLFRKSNLK PFERDISTEI YQAGSKPCNG VEGFNCYFPL QSYGFQPTNG VGYQP YRVV VLSFELLHAP ATVCGPKKST NLVKNKCVNF NFNGLTGTGV LTESNKKFLP FQQFGRDIAD TTDAVRDPQT LEILDI TPC SFGGVSVITP GTNTSNQVAV LYQGVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY ECDIPIG AG ICASYQTQTN SPGSASSVAS QSIIAYTMSL GAENSVAYSN NSIAIPTNFT ISVTTEILPV SMTKTSVDCT MYICGDST E CSNLLLQYGS FCTQLNRALT GIAVEQDKNT QEVFAQVKQI YKTPPIKDFG GFNFSQILPD PSKPSKRSFI EDLLFNKVT LADAGFIKQY GDCLGDIAAR DLICAQKFNG LTVLPPLLTD EMIAQYTSAL LAGTITSGWT FGAGPALQIP FPMQMAYRFN GIGVTQNVL YENQKLIANQ FNSAIGKIQD SLSSTPSALG KLQNVVNQNA QALNTLVKQL SSNFGAISSV LNDILSRLDP P EAEVQIDR LITGRLQSLQ TYVTQQLIRA AEIRASANLA ATKMSECVLG QSKRVDFCGK GYHLMSFPQS APHGVVFLHV TY VPAQEKN FTTAPAICHD GKAHFPREGV FVSNGTHWFV TQRNFYEPQI ITTDNTFVSG NCDVVIGIVN NTVYDPLQP |
-Macromolecule #2: BA7125 fab
Macromolecule | Name: BA7125 fab / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.882381 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVMTQSPGT LSLSPGERAT LSCRASQSIS SSYLAWFQQK PGQAPRLLIY GASSRAPGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGDSPLTF GGGTKVDIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVMTQSPGT LSLSPGERAT LSCRASQSIS SSYLAWFQQK PGQAPRLLIY GASSRAPGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGDSPLTF GGGTKVDIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFN |
-Macromolecule #3: BA7125 fab
Macromolecule | Name: BA7125 fab / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.978664 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLQQWGAG LLKPSETLSL TCAVYGESFS GYYWSWIRQS PGKGLEWIGQ INHSGNTNYN PSLKSRVTMS VDTSKNQFSL KLSSVTAAD TAVYYCAREL GHDYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA L TSGVHTFP ...String: EVQLQQWGAG LLKPSETLSL TCAVYGESFS GYYWSWIRQS PGKGLEWIGQ INHSGNTNYN PSLKSRVTMS VDTSKNQFSL KLSSVTAAD TAVYYCAREL GHDYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA L TSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPK |
-Macromolecule #4: BA7208 fab
Macromolecule | Name: BA7208 fab / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.515722 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASSLESGVPS RFSGSGSGTE FTLTITSLQP DDFATYYCQ QYDSFSWTFG QGTKLE |
-Macromolecule #5: BA7208 fab
Macromolecule | Name: BA7208 fab / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.397985 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVQSGAE VKKPGESLKI SCKGSGYSFT SYYWIGWVRQ MPGKGLEWMG IVYPDDSDTR YSPSFQGQVT ISADKSISTA YLQWSSLKA SDTAMYYCVR HPGGGDWYFD LWGRGTLVTV S |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 12 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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: 1.39 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: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.08 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 223225 |
---|---|
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |