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Yorodumi- EMDB-35932: Local refined cryo-EM reconstruction of Omicron BA.5 RBD in compl... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35932 | |||||||||
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Title | Local refined cryo-EM reconstruction of Omicron BA.5 RBD in complex with 8-9D Fab | |||||||||
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / 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: 3.3 Å | |||||||||
Authors | Xiang Y / Li R | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection. Authors: Wanbo Tai / Kai Yang / Yubin Liu / Ruofan Li / Shengyong Feng / Benjie Chai / Xinyu Zhuang / Shaolong Qi / Huicheng Shi / Zhida Liu / Jiaqi Lei / Enhao Ma / Weixiao Wang / Chongyu Tian / ...Authors: Wanbo Tai / Kai Yang / Yubin Liu / Ruofan Li / Shengyong Feng / Benjie Chai / Xinyu Zhuang / Shaolong Qi / Huicheng Shi / Zhida Liu / Jiaqi Lei / Enhao Ma / Weixiao Wang / Chongyu Tian / Ting Le / Jinyong Wang / Yunfeng Chen / Mingyao Tian / Ye Xiang / Guocan Yu / Gong Cheng / Abstract: The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by ...The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35932.map.gz | 190.4 MB | EMDB map data format | |
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Header (meta data) | emd-35932-v30.xml emd-35932.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35932_fsc.xml | 12.6 KB | Display | FSC data file |
Images | emd_35932.png | 36.4 KB | ||
Masks | emd_35932_msk_1.map | 216 MB | Mask map | |
Filedesc metadata | emd-35932.cif.gz | 5.9 KB | ||
Others | emd_35932_half_map_1.map.gz emd_35932_half_map_2.map.gz | 200 MB 200 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35932 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35932 | HTTPS FTP |
-Validation report
Summary document | emd_35932_validation.pdf.gz | 688.9 KB | Display | EMDB validaton report |
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Full document | emd_35932_full_validation.pdf.gz | 688.5 KB | Display | |
Data in XML | emd_35932_validation.xml.gz | 21.4 KB | Display | |
Data in CIF | emd_35932_validation.cif.gz | 27.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35932 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35932 | HTTPS FTP |
-Related structure data
Related structure data | 8j1tMC 8j1vC 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_35932.map.gz / Format: CCP4 / Size: 216 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: 0.97 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_35932_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35932_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35932_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 RBD ...
Entire | Name: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 RBD bound 8-9D Fab |
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Components |
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-Supramolecule #1: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 RBD ...
Supramolecule | Name: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 RBD bound 8-9D Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22 KDa |
-Supramolecule #2: 8-9D Fab
Supramolecule | Name: 8-9D Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: SARS-CoV2 Omicron BA.5 RBD
Supramolecule | Name: SARS-CoV2 Omicron BA.5 RBD / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: 8-9D heavy chain
Macromolecule | Name: 8-9D heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.439867 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQLVESGGGL VQPGGSLRLS CAASGLTVSS NYMNWVRQAP GKGLEWVSVF YPGGSTFYAD SVRGRFTISR DNSKNTLYLQ MNSLRAEDT AVYYCARDHS GHALDIWGQG TMVTVS |
-Macromolecule #2: 8-9D light chain
Macromolecule | Name: 8-9D 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: 11.729067 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKP GKAPKLLIYA ASTLQSGVPS RFSGSGSGTE FTLTISSLQP EDFATYYCQ HLNSYPSMYT FGQGTKVDI |
-Macromolecule #3: Spike protein
Macromolecule | Name: Spike protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 21.905697 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNFAP FFAFKCYGVS PTKLNDLCFT NVYADSFVIR GNEVSQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVGGNYNYR YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGVNCYFPL Q SYGFRPTY ...String: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNFAP FFAFKCYGVS PTKLNDLCFT NVYADSFVIR GNEVSQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVGGNYNYR YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGVNCYFPL Q SYGFRPTY GVGHQPYRVV VLSFELLHAP ATVCGP UniProtKB: Spike glycoprotein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.7 |
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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 (6k x 4k) / Average electron dose: 50.0 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: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | PDB-8j1t: |