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Yorodumi- PDB-8k3k: The crystal structure of nanobody Nb4 in complex with receptor bi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8k3k | ||||||
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Title | The crystal structure of nanobody Nb4 in complex with receptor binding domain (RBD) of BA.1 Spike protein | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Nanobody / Receptor binding domain / SARS-CoV-2 / Complex / VIRAL PROTEIN / 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 synthetic construct (others) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.43 Å | ||||||
Authors | Wang, H.Y. / Xu, W.Q. | ||||||
Funding support | China, 1items
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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 | 8k3k.cif.gz | 153.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8k3k.ent.gz | 119.7 KB | Display | PDB format |
PDBx/mmJSON format | 8k3k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8k3k_validation.pdf.gz | 448.5 KB | Display | wwPDB validaton report |
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Full document | 8k3k_full_validation.pdf.gz | 453 KB | Display | |
Data in XML | 8k3k_validation.xml.gz | 14 KB | Display | |
Data in CIF | 8k3k_validation.cif.gz | 18.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k3/8k3k ftp://data.pdbj.org/pub/pdb/validation_reports/k3/8k3k | HTTPS FTP |
-Related structure data
Related structure data | 8k45C 8k46C 8k47C 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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Unit cell |
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-Components
#1: Protein | Mass: 28329.930 Da / Num. of mol.: 1 / Fragment: receptor binding domain (RBD) Source method: isolated from a genetically manipulated source Details: Omicron BA.1 Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2 |
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#2: Antibody | Mass: 17057.576 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli MC1061 (bacteria) |
#3: Water | ChemComp-HOH / |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.32 Å3/Da / Density % sol: 46.89 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / Details: 0.2 M potassium thiocyanate, 20 %(w/v) PEG 3350 |
-Data collection
Diffraction | Mean temperature: 77.15 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: NFPSS / Beamline: BL19U1 / Wavelength: 0.9792 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Aug 1, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 |
Reflection | Resolution: 2.43→35.37 Å / Num. obs: 30440 / % possible obs: 100 % / Redundancy: 36.8 % / CC1/2: 0.997 / Net I/σ(I): 14.8 |
Reflection shell | Resolution: 2.43→2.49 Å / Num. unique obs: 828 / CC1/2: 0.706 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.43→35.37 Å / SU ML: 0.43 / Cross valid method: NONE / σ(F): 1.34 / Phase error: 30.33 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.43→35.37 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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