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Yorodumi- PDB-8k46: A potent and broad-spectrum neutralizing nanobody for SARS-CoV-2 ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8k46 | |||||||||
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Title | A potent and broad-spectrum neutralizing nanobody for SARS-CoV-2 viruses including all major Omicron strains | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / spike glycoprotein / virus / antibody / 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 | Vicugna pacos (alpaca) Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.37 Å | |||||||||
Authors | Lu, Y. / Gao, Y. / Yao, H. / Xu, W. / Yang, H. | |||||||||
Funding support | 2items
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Citation | Journal: MedComm (2020) / Year: 2023 Title: A potent and broad-spectrum neutralizing nanobody for SARS-CoV-2 viruses, including all major Omicron strains. Authors: Hebang Yao / Hongyang Wang / Zhaoyong Zhang / Yuchi Lu / Zhiying Zhang / Yu Zhang / Xinyi Xiong / Yanqun Wang / Zhizhi Wang / Haitao Yang / Jincun Zhao / Wenqing Xu / Abstract: SARS-CoV-2 viruses are highly transmissible and immune evasive. It is critical to develop broad-spectrum prophylactic and therapeutic antibodies for potential future pandemics. Here, we used the ...SARS-CoV-2 viruses are highly transmissible and immune evasive. It is critical to develop broad-spectrum prophylactic and therapeutic antibodies for potential future pandemics. Here, we used the phage display method to discover nanobodies (Nbs) for neutralizing SARS-CoV-2 viruses especially Omicron strains. The leading nanobody (Nb), namely, Nb4, with excellent physicochemical properties, can neutralize Delta and Omicron subtypes, including BA.1, BA.1.1 (BA.1 + R346K), BA.2, BA.5, BQ.1, and XBB.1. The crystal structure of Nb4 in complex with the receptor-binding domain (RBD) of BA.1 Spike protein reveals that Nb4 interacts with an epitope on the RBD overlapping with the receptor-binding motif, and thus competes with angiotensin-converting enzyme 2 (ACE2) binding. Nb4 is expected to be effective for neutralizing most recent Omicron variants, since the epitopes are evolutionarily conserved among them. Indeed, trivalent Nb4 interacts with the XBB1.5 Spike protein with low nM affinity and competes for ACE2 binding. Prophylactic and therapeutic experiments in mice indicated that Nb4 could reduce the Omicron virus loads in the lung. In particular, in prophylactic experiments, intranasal administration of multivalent Nb4 completely protected mice from Omicron infection. Taken together, these results demonstrated that Nb4 could serve as a potent and broad-spectrum prophylactic and therapeutic Nb for COVID-19. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8k46.cif.gz | 724.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8k46.ent.gz | 587.3 KB | Display | PDB format |
PDBx/mmJSON format | 8k46.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8k46_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8k46_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8k46_validation.xml.gz | 81.3 KB | Display | |
Data in CIF | 8k46_validation.cif.gz | 121.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k4/8k46 ftp://data.pdbj.org/pub/pdb/validation_reports/k4/8k46 | HTTPS FTP |
-Related structure data
Related structure data | 36878MC 8k3kC 8k45C 8k47C 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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1 |
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-Components
#1: Antibody | Mass: 13911.263 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Escherichia coli (E. coli) #2: Protein | Mass: 142592.938 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Strain: strain: Omicron / Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #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
Component | Name: SARS-CoV-2 Omicron BA.1 Spike glycoprotein complex with Nb4 nanobody Type: COMPLEX / Entity ID: #2, #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.37 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 60877 / Symmetry type: POINT | ||||||||||||||||||||||||
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