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- PDB-7vnb: Crystal structure of the SARS-CoV-2 RBD in complex with a human s... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7vnb | ||||||
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Title | Crystal structure of the SARS-CoV-2 RBD in complex with a human single domain antibody n3113 | ||||||
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![]() | VIRAL PROTEIN / SARS-CoV-2 / nanobody | ||||||
Function / homology | ![]() 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / 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 | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Yang, Z. / Wang, Y. / Kong, Y. / Jin, Y. / Wu, Y. / Ying, T. | ||||||
Funding support | ![]()
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![]() | ![]() Title: A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants. Authors: Zhenlin Yang / Yulu Wang / Yujia Jin / Yuanfei Zhu / Yanling Wu / Cheng Li / Yu Kong / Wenping Song / Xiaolong Tian / Wuqiang Zhan / Ailing Huang / Shanshan Zhou / Shuai Xia / Xiaoxu Tian / ...Authors: Zhenlin Yang / Yulu Wang / Yujia Jin / Yuanfei Zhu / Yanling Wu / Cheng Li / Yu Kong / Wenping Song / Xiaolong Tian / Wuqiang Zhan / Ailing Huang / Shanshan Zhou / Shuai Xia / Xiaoxu Tian / Chao Peng / Cuicui Chen / Yibing Shi / Gaowei Hu / Shujuan Du / Yuyan Wang / Youhua Xie / Shibo Jiang / Lu Lu / Lei Sun / Yuanlin Song / Tianlei Ying / ![]() Abstract: The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for ...The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 104.6 KB | Display | ![]() |
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PDB format | ![]() | 63.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 459.3 KB | Display | ![]() |
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Full document | ![]() | 461.4 KB | Display | |
Data in XML | ![]() | 16.9 KB | Display | |
Data in CIF | ![]() | 24.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vncC ![]() 7vndC ![]() 7vneC ![]() 6lzgS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 12963.374 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 24966.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Production host: ![]() ![]() |
#3: Sugar | ChemComp-NAG / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 5.05 Å3/Da / Density % sol: 75.63 % |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, sitting drop / Details: 4.3M sodium chloride and 0.1M HEPES, pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 7, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 2.27→73.11 Å / Num. obs: 34264 / % possible obs: 99.9 % / Redundancy: 10.4 % / Biso Wilson estimate: 37.75 Å2 / CC1/2: 0.997 / Net I/σ(I): 11.1 |
Reflection shell | Resolution: 2.27→2.33 Å / Num. unique obs: 2535 / CC1/2: 0.798 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6LZG Resolution: 2.27→42.56 Å / SU ML: 0.2658 / Cross valid method: FREE R-VALUE / σ(F): 1.97 / Phase error: 23.9074
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 40.35 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.27→42.56 Å
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Refine LS restraints |
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LS refinement shell |
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