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Yorodumi- EMDB-33142: Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33142 | |||||||||
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Title | Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex with BA7208 fab | |||||||||
Map data | ||||||||||
Sample |
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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 / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.62 Å | |||||||||
Authors | Liu Z / Liu S / Gao YZ | |||||||||
Funding support | China, 1 items
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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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33142.map.gz | 230.1 MB | EMDB map data format | |
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Header (meta data) | emd-33142-v30.xml emd-33142.xml | 19.2 KB 19.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_33142_fsc.xml | 13.2 KB | Display | FSC data file |
Images | emd_33142.png | 85.5 KB | ||
Others | emd_33142_half_map_1.map.gz emd_33142_half_map_2.map.gz | 226.8 MB 226.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33142 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33142 | HTTPS FTP |
-Related structure data
Related structure data | 7xdbMC 7xczC 7xdaC 7xdkC 7xdlC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33142.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.856 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33142_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33142_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex ...
Entire | Name: Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex with BA7208 fab |
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Components |
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-Supramolecule #1: Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex ...
Supramolecule | Name: Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex with BA7208 fab type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: BA7208 fab
Supramolecule | Name: BA7208 fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1, #3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: SARS-CoV-2 Omicron Spike protein
Supramolecule | Name: SARS-CoV-2 Omicron Spike protein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: BA7208 fab
Macromolecule | Name: BA7208 fab / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.62888 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASSLESGVPS RFSGSGSGTE FTLTITSLQP DDFATYYCQ QYDSFSWTFG QGTKLEI |
-Macromolecule #2: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 124.03693 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: PAYTNSFTRG VYYPDKVFRS SVLHSTQDLF LPFFSNVTWF HVISGTNGTK RFDNPVLPFN DGVYFASIEK SNIIRGWIFG TTLDSKTQS LLIVNNATNV VIKVCEFQFC NDPFLDHKNN KSWMESEFRV YSSANNCTFE YVSQPFLMDL EGKQGNFKNL R EFVFKNID ...String: PAYTNSFTRG VYYPDKVFRS SVLHSTQDLF LPFFSNVTWF HVISGTNGTK RFDNPVLPFN DGVYFASIEK SNIIRGWIFG TTLDSKTQS LLIVNNATNV VIKVCEFQFC NDPFLDHKNN KSWMESEFRV YSSANNCTFE YVSQPFLMDL EGKQGNFKNL R EFVFKNID GYFKIYSKHT PIIVREPEDL PQGFSALEPL VDLPIGINIT RFQTLLALHR SYLTPGDSSS GWTAGAAAYY VG YLQPRTF LLKYNENGTI TDAVDCALDP LSETKCTLKS FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPFDEVFNAT RFA SVYAWN RKRISNCVAD YSVLYNLAPF FTFKCYGVSP TKLNDLCFTN VYADSFVIRG DEVRQIAPGQ TGNIADYNYK LPDD FTGCV IAWNSNKLDS KVSGNYNYLY RLFRKSNLKP FERDISTEIY QAGNKPCNGV AGFNCYFPLR SYSFRPTYGV GHQPY RVVV LSFELLHAPA TVCGPKKSTN LVKNKCVNFN FNGLKGTGVL TESNKKFLPF QQFGRDIADT TDAVRDPQTL EILDIT PCS FGGVSVITPG TNTSNQVAVL YQGVNCTEVP VAIHADQLTP TWRVYSTGSN VFQTRAGCLI GAEYVNNSYE CDIPIGA GI CASYQTQTNS PRRARSVASQ SIIAYTMSLG AENSVAYSNN SIAIPTNFTI SVTTEILPVS MTKTSVDCTM YICGDSTE C SNLLLQYGSF CTQLKRALTG IAVEQDKNTQ EVFAQVKQIY KTPPIKYFGG FNFSQILPDP SKPSKRSPIE DLLFNKVTL ADAGFIKQYG DCLGDIAARD LICAQKFKGL TVLPPLLTDE MIAQYTSALL AGTITSGWTF GAGPALQIPF PMQMAYRFNG IGVTQNVLY ENQKLIANQF NSAIGKIQDS LSSTPSALGK LQDVVNHNAQ ALNTLVKQLS SKFGAISSVL NDIFSRLDPP E AEVQIDRL ITGRLQSLQT YVTQQLIRAA EIRASANLAA TKMSECVLGQ SKRVDFCGKG YHLMSFPQSA PHGVVFLHVT YV PAQEKNF TTAPAICHDG KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDVVIGIVNN TVYDPLQPE |
-Macromolecule #3: BA7208 fab
Macromolecule | Name: BA7208 fab / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.181793 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQLVQSGAEV KKPGESLKIS CKGSGYSFTS YYWIGWVRQM PGKGLEWMGI VYPDDSDTRY SPSFQGQVTI SADKSISTAY LQWSSLKAS DTAMYYCVRH PGGGDWYFDL WGRGTLVTV |
-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: 16 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.39 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |