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Yorodumi- PDB-8j1v: Cryo-EM structure of SARS-CoV2 Omicron BA.5 spike in complex with... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8j1v | ||||||
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Title | Cryo-EM structure of SARS-CoV2 Omicron BA.5 spike in complex with 8-9D Fabs | ||||||
Components |
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Keywords | 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 / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å | ||||||
Authors | Xiang, Y. / Li, R. | ||||||
Funding support | China, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8j1v.cif.gz | 687.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8j1v.ent.gz | 551.8 KB | Display | PDB format |
PDBx/mmJSON format | 8j1v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8j1v_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8j1v_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8j1v_validation.xml.gz | 112.4 KB | Display | |
Data in CIF | 8j1v_validation.cif.gz | 166.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j1/8j1v ftp://data.pdbj.org/pub/pdb/validation_reports/j1/8j1v | HTTPS FTP |
-Related structure data
Related structure data | 35934MC 8j1tC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 123511.086 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 12439.867 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) #3: Antibody | Mass: 11729.067 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) #4: Sugar | ChemComp-NAG / Has ligand of interest | N | Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Details of virus | Empty: NO / Enveloped: NO / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE | ||||||||||||||||||||||||
Natural host | Organism: Homo sapiens | ||||||||||||||||||||||||
Buffer solution | pH: 7.7 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 296568 / Symmetry type: POINT |
Atomic model building | Protocol: FLEXIBLE FIT |