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Yorodumi- EMDB-36672: Cryo-EM structure of the N-terminal domain of Omicron BA.1 in com... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36672 | |||||||||
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Title | Cryo-EM structure of the N-terminal domain of Omicron BA.1 in complex with nanobody N235 and S2L20 Fab | |||||||||
Map data | ||||||||||
Sample |
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Keywords | complex / 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 / 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 / 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 | Vicugna pacos (alpaca) / Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.81 Å | |||||||||
Authors | Liu B / Liu HH / Han P / Qi JX | |||||||||
Funding support | China, 1 items
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Citation | Journal: Signal Transduct Target Ther / Year: 2024 Title: Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain. Authors: Bo Liu / Honghui Liu / Pu Han / Xiaoyun Wang / Chunmei Wang / Xinxin Yan / Wenwen Lei / Ke Xu / Jianjie Zhou / Jianxun Qi / Ruiwen Fan / Guizhen Wu / Wen-Xia Tian / George F Gao / Qihui Wang / Abstract: Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS- ...Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36672.map.gz | 250.6 MB | EMDB map data format | |
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Header (meta data) | emd-36672-v30.xml emd-36672.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36672_fsc.xml | 17 KB | Display | FSC data file |
Images | emd_36672.png | 46.9 KB | ||
Filedesc metadata | emd-36672.cif.gz | 6.3 KB | ||
Others | emd_36672_half_map_1.map.gz emd_36672_half_map_2.map.gz | 475.8 MB 475.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36672 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36672 | HTTPS FTP |
-Validation report
Summary document | emd_36672_validation.pdf.gz | 853.6 KB | Display | EMDB validaton report |
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Full document | emd_36672_full_validation.pdf.gz | 853.1 KB | Display | |
Data in XML | emd_36672_validation.xml.gz | 26.6 KB | Display | |
Data in CIF | emd_36672_validation.cif.gz | 34.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36672 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36672 | HTTPS FTP |
-Related structure data
Related structure data | 8jvaMC 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_36672.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.54 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36672_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36672_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : the N-terminal domain of Omicron BA.1 in complex with nanobody N2...
Entire | Name: the N-terminal domain of Omicron BA.1 in complex with nanobody N235 and S2L20 Fab |
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Components |
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-Supramolecule #1: the N-terminal domain of Omicron BA.1 in complex with nanobody N2...
Supramolecule | Name: the N-terminal domain of Omicron BA.1 in complex with nanobody N235 and S2L20 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Vicugna pacos (alpaca) |
-Macromolecule #1: nanobody N235
Macromolecule | Name: nanobody N235 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Vicugna pacos (alpaca) |
Molecular weight | Theoretical: 13.970428 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGLIIS RYDMSWYRQA PGKERELVAT TPIPAARPQY ADSVKGRFTI SRDNAKNTVS LQMNSLKPE DTAVYYCNLG PESQDHNYNY WGQGTQVTVS SHHHHHH |
-Macromolecule #2: S2L20 light chain
Macromolecule | Name: S2L20 light chain / 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: 26.017973 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: METDTLLLWV LLLWVPGSTG DVIWMTQSPS SLSASVGDRV TITCQASQDI RFYLNWYQQK PGKAPKLLIS DASNMETGVP SRFSGSGSG TDFTFTISSL QPEDIATYYC QQYDNLPFTF GPGTKVDFKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN F YPREAKVQ ...String: METDTLLLWV LLLWVPGSTG DVIWMTQSPS SLSASVGDRV TITCQASQDI RFYLNWYQQK PGKAPKLLIS DASNMETGVP SRFSGSGSG TDFTFTISSL QPEDIATYYC QQYDNLPFTF GPGTKVDFKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN F YPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGECS |
-Macromolecule #3: S2L20 heavy chain
Macromolecule | Name: S2L20 heavy chain / 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: 52.041504 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: METDTLLLWV LLLWVPGSTG DEVQLVESGG GVVQPGGSLR LSCAASGFTF NSYGMHWVRQ APGKGLEWVA FIRYDGGNKY YADSVKGRF TISRDNSKNT LYLQMKSLRA EDTAVYYCAN LKDSRYSGSY YDYWGQGTLV TVSSASTKGP SVFPLAPSSK S TSGGTAAL ...String: METDTLLLWV LLLWVPGSTG DEVQLVESGG GVVQPGGSLR LSCAASGFTF NSYGMHWVRQ APGKGLEWVA FIRYDGGNKY YADSVKGRF TISRDNSKNT LYLQMKSLRA EDTAVYYCAN LKDSRYSGSY YDYWGQGTLV TVSSASTKGP SVFPLAPSSK S TSGGTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KR VEPKSCD KTHTCPPCPA PELLGGPSVF LFPPKPKDTL MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP REE QYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK GFYP SDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK |
-Macromolecule #4: Spike protein S2'
Macromolecule | Name: Spike protein S2' / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 / Strain: Omicron/BA.1 |
Molecular weight | Theoretical: 34.076633 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIVR EPEDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTL UniProtKB: Spike glycoprotein |
-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: 5 / 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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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 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: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |