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Yorodumi- EMDB-34526: Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 f... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34526 | |||||||||
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Title | Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 fab (local refinement) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | 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: 3.07 Å | |||||||||
Authors | Liu Z / Yan A / Gao Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants. Authors: Yanqun Wang / An Yan / Deyong Song / Maoqin Duan / Chuangchuang Dong / Jiantao Chen / Zihe Jiang / Yuanzhu Gao / Muding Rao / Jianxia Feng / Zhaoyong Zhang / Ruxi Qi / Xiaomin Ma / Hong Liu ...Authors: Yanqun Wang / An Yan / Deyong Song / Maoqin Duan / Chuangchuang Dong / Jiantao Chen / Zihe Jiang / Yuanzhu Gao / Muding Rao / Jianxia Feng / Zhaoyong Zhang / Ruxi Qi / Xiaomin Ma / Hong Liu / Beibei Yu / Qiaoping Wang / Mengqi Zong / Jie Jiao / Pingping Xing / Rongrong Pan / Dan Li / Juxue Xiao / Junbo Sun / Ying Li / Linfeng Zhang / Zhenduo Shen / Baiping Sun / Yanyan Zhao / Lu Zhang / Jun Dai / Jingxian Zhao / Lan Wang / Changlin Dou / Zheng Liu / Jincun Zhao / Abstract: The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. ...The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_34526.map.gz | 59.5 MB | EMDB map data format | |
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Header (meta data) | emd-34526-v30.xml emd-34526.xml | 17.2 KB 17.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_34526_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_34526.png | 76.4 KB | ||
Filedesc metadata | emd-34526.cif.gz | 6 KB | ||
Others | emd_34526_half_map_1.map.gz emd_34526_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34526 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34526 | HTTPS FTP |
-Validation report
Summary document | emd_34526_validation.pdf.gz | 809.2 KB | Display | EMDB validaton report |
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Full document | emd_34526_full_validation.pdf.gz | 808.8 KB | Display | |
Data in XML | emd_34526_validation.xml.gz | 16.2 KB | Display | |
Data in CIF | emd_34526_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34526 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34526 | HTTPS FTP |
-Related structure data
Related structure data | 8h7zMC 8h7lC 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_34526.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.336 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34526_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34526_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 BA.2 RBD in complex with BA7535 f...
Entire | Name: Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 fab (local refinement) |
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Components |
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-Supramolecule #1: Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 f...
Supramolecule | Name: Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 fab (local refinement) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22.282211 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ITNLCPFDEV FNATRFASVY AWNRKRISNC VADYSVLYNF APFFAFKCYG VSPTKLNDLC FTNVYADSFV IRGNEVSQIA PGQTGNIAD YNYKLPDDFT GCVIAWNSNK LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGNKPC NGVAGFNCYF P LRSYGFRP ...String: ITNLCPFDEV FNATRFASVY AWNRKRISNC VADYSVLYNF APFFAFKCYG VSPTKLNDLC FTNVYADSFV IRGNEVSQIA PGQTGNIAD YNYKLPDDFT GCVIAWNSNK LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGNKPC NGVAGFNCYF P LRSYGFRP TYGVGHQPYR VVVLSFELLH APATVCGPK UniProtKB: Spike glycoprotein |
-Macromolecule #2: BA7535 fab
Macromolecule | Name: BA7535 fab / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 49.838086 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG VVQPGRSLRL SCAASEFTFS SFAMHWVRQA PGKGLEWVAL ISYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCARV SYPLTKYYYG MDVWGQGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: EVQLVESGGG VVQPGRSLRL SCAASEFTFS SFAMHWVRQA PGKGLEWVAL ISYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCARV SYPLTKYYYG MDVWGQGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK THTCPPCPAP EL LGGPSVF LFPPKPKDTL MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP REEQYNSTYR VVSVLTVLHQ DWL NGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTT PPVLD SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK |
-Macromolecule #3: BA7535 fab
Macromolecule | Name: BA7535 fab / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.431002 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVMTQSPAF MSATPGDKVN ISCKASQDIA DDMNWYQQKP GEAAIFIIQE ATTLVPGISP RFSGSGYGTD FTLTINNIES EDAAYYFCL QHDNFPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: EIVMTQSPAF MSATPGDKVN ISCKASQDIA DDMNWYQQKP GEAAIFIIQE ATTLVPGISP RFSGSGYGTD FTLTINNIES EDAAYYFCL QHDNFPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-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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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 |