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Yorodumi- EMDB-35934: Cryo-EM reconstruction of SARS-CoV2 Omicron BA.5 spike in complex... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35934 | |||||||||
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Title | Cryo-EM reconstruction of SARS-CoV2 Omicron BA.5 spike in complex with 8-9D Fabs | |||||||||
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: 3.01 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_35934.map.gz | 189.7 MB | EMDB map data format | |
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Header (meta data) | emd-35934-v30.xml emd-35934.xml | 18.8 KB 18.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35934_fsc.xml | 12.7 KB | Display | FSC data file |
Images | emd_35934.png | 39.6 KB | ||
Filedesc metadata | emd-35934.cif.gz | 6.8 KB | ||
Others | emd_35934_half_map_1.map.gz emd_35934_half_map_2.map.gz | 200.4 MB 200.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35934 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35934 | HTTPS FTP |
-Related structure data
Related structure data | 8j1vMC 8j1tC 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_35934.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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
-Half map: #1
File | emd_35934_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35934_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 spik...
Entire | Name: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 spike bound 8-9D Fab |
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Components |
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-Supramolecule #1: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 spik...
Supramolecule | Name: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 spike bound 8-9D Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 369 KDa |
-Supramolecule #2: 8-9D Fab variable region
Supramolecule | Name: 8-9D Fab variable region / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: SARS-CoV2 Omicron BA.5 spike ectodomain
Supramolecule | Name: SARS-CoV2 Omicron BA.5 spike ectodomain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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-Macromolecule #1: Spike protein S2'
Macromolecule | Name: Spike protein S2' / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 123.511086 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TQSYTNSFTR GVYYPDKVFR SSVLHSTQDL FLPFFSNVTW FHAISGTNGT KRFDNPVLPF NDGVYFASTE KSNIIRGWIF GTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLDVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN F KNLREFVF ...String: TQSYTNSFTR GVYYPDKVFR SSVLHSTQDL FLPFFSNVTW FHAISGTNGT KRFDNPVLPF NDGVYFASTE KSNIIRGWIF GTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLDVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN F KNLREFVF KNIDGYFKIY SKHTPINLGR DLPQGFSALE PLVDLPIGIN ITRFQTLLAL HRSYLTPGDS SSGWTAGAAA YY VGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFDEVFN ATR FASVYA WNRKRISNCV ADYSVLYNFA PFFAFKCYGV SPTKLNDLCF TNVYADSFVI RGNEVSQIAP GQTGNIADYN YKLP DDFTG CVIAWNSNKL DSKVGGNYNY RYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGVNCYFP LQSYGFRPTY GVGHQ PYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILD ITP CSFGGVSVIT PGTNTSNQVA VLYQGVNCTE VPVAIHADQL TPTWRVYSTG SNVFQTRAGC LIGAEYVNNS YECDIPI GA GICASYQTQT KSHGSASSVA SQSIIAYTMS LGAENSVAYS NNSIAIPTNF TISVTTEILP VSMTKTSVDC TMYICGDS T ECSNLLLQYG SFCTQLKRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKYF GGFNFSQILP DPSKPSKRSP IEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGPALQI PFPMQMAYRF NGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNHN AQALNTLVKQ LSSKFGAISS VLNDILSRLD P PEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SAPHGVVFLH VT YVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPL UniProtKB: Spike glycoprotein |
-Macromolecule #2: 8-9D heavy chain
Macromolecule | Name: 8-9D heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / 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 #3: 8-9D light chain
Macromolecule | Name: 8-9D light chain / 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: 11.729067 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKP GKAPKLLIYA ASTLQSGVPS RFSGSGSGTE FTLTISSLQP EDFATYYCQ HLNSYPSMYT FGQGTKVDI |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 27 / 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: 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-8j1v: |