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Yorodumi- EMDB-36730: SARS-CoV-2 Spike RBD (dimer) in complex with two 2S-1244 nanobodies -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36730 | |||||||||
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Title | SARS-CoV-2 Spike RBD (dimer) in complex with two 2S-1244 nanobodies | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Spike / nanobody / dimer / local / VIRAL PROTEIN | |||||||||
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 | Camelus bactrianus (Bactrian camel) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.5 Å | |||||||||
Authors | Yang Y / Zhang CH | |||||||||
Funding support | China, 1 items
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Citation | Journal: Exploration (Beijing) / Year: 2024 Title: A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation. Authors: Yang Yang / Junfang Zhang / Shengnan Zhang / Chenhui Zhang / Chenguang Shen / Shuo Song / Yanqun Wang / Yun Peng / Xiaohua Gong / Jun Dai / Chongwei Xie / Tatyana Aleksandrovna Khrustaleva / ...Authors: Yang Yang / Junfang Zhang / Shengnan Zhang / Chenhui Zhang / Chenguang Shen / Shuo Song / Yanqun Wang / Yun Peng / Xiaohua Gong / Jun Dai / Chongwei Xie / Tatyana Aleksandrovna Khrustaleva / Vladislav Victorovich Khrustalev / Yongting Huo / Di Lu / Da Yao / Jincun Zhao / Yingxia Liu / Hongzhou Lu / Abstract: The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a ...The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT-CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo-EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the "up" state and bound by six VHHs. IBT-CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT-CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next-generation vaccines. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36730.map.gz | 20.9 MB | EMDB map data format | |
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Header (meta data) | emd-36730-v30.xml emd-36730.xml | 17.1 KB 17.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36730_fsc.xml | 6 KB | Display | FSC data file |
Images | emd_36730.png | 43.1 KB | ||
Filedesc metadata | emd-36730.cif.gz | 5.7 KB | ||
Others | emd_36730_half_map_1.map.gz emd_36730_half_map_2.map.gz | 20.7 MB 20.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36730 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36730 | HTTPS FTP |
-Validation report
Summary document | emd_36730_validation.pdf.gz | 781 KB | Display | EMDB validaton report |
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Full document | emd_36730_full_validation.pdf.gz | 780.5 KB | Display | |
Data in XML | emd_36730_validation.xml.gz | 13.3 KB | Display | |
Data in CIF | emd_36730_validation.cif.gz | 16.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36730 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36730 | HTTPS FTP |
-Related structure data
Related structure data | 8jysMC 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_36730.map.gz / Format: CCP4 / Size: 22.2 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: 0.842 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36730_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36730_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : complex of RBD domain of SARS-CoV-2 spike protein and IBT-CoV144
Entire | Name: complex of RBD domain of SARS-CoV-2 spike protein and IBT-CoV144 |
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Components |
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-Supramolecule #1: complex of RBD domain of SARS-CoV-2 spike protein and IBT-CoV144
Supramolecule | Name: complex of RBD domain of SARS-CoV-2 spike protein and IBT-CoV144 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Camelus bactrianus (Bactrian camel) |
-Macromolecule #1: IBT-CoV144 nanobody
Macromolecule | Name: IBT-CoV144 nanobody / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Camelus bactrianus (Bactrian camel) |
Molecular weight | Theoretical: 15.539212 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVESGGG PVQAGGSLRL SCTCSRCTFN WDGMGWFRQA PGKEREFVAT ISWSGQEPAY ADSVKGRFTI SRDKPKNTVY LQMTSLKSE DTAVYYCAAA QYTGASYSIL RDQVGYDYWG QGTRVTVSAE PKTPKPQDGQ AGQ |
-Macromolecule #2: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22.169053 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TNLCPFDEVF NATRFASVYA WNRKRISNCV ADYSVLYNFA PFFAFKCYGV SPTKLNDLCF TNVYADSFVI RGNEVSQIAP GQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGFNCYFP L RSYGFRPT ...String: TNLCPFDEVF NATRFASVYA WNRKRISNCV ADYSVLYNFA PFFAFKCYGV SPTKLNDLCF TNVYADSFVI RGNEVSQIAP GQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGFNCYFP L RSYGFRPT YGVGHQPYRV VVLSFELLHA PATVCGPK UniProtKB: Spike glycoprotein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.2 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 75 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 93.0 K / Max: 93.0 K |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated defocus max: 2.5 µm / Calibrated defocus min: 1.5 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |