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- PDB-7ttm: Crystal structure of potent neutralizing antibody 10-40 in comple... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7ttm | ||||||
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Title | Crystal structure of potent neutralizing antibody 10-40 in complex with Sarbecovirus bat SHC014 receptor-binding domain | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / SarbecoVirus / SCH014 RBD / Viral protein / Spike glycoprotein / Receptor Binding Protein / Neutralizing antibody / potent / 10-40 / Fab / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Reddem, E.R. / Shapiro, L. | ||||||
Funding support | ![]()
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![]() | ![]() Title: An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses. Authors: Lihong Liu / Sho Iketani / Yicheng Guo / Eswar R Reddem / Ryan G Casner / Manoj S Nair / Jian Yu / Jasper F-W Chan / Maple Wang / Gabriele Cerutti / Zhiteng Li / Nicholas C Morano / Candace ...Authors: Lihong Liu / Sho Iketani / Yicheng Guo / Eswar R Reddem / Ryan G Casner / Manoj S Nair / Jian Yu / Jasper F-W Chan / Maple Wang / Gabriele Cerutti / Zhiteng Li / Nicholas C Morano / Candace D Castagna / Laura Corredor / Hin Chu / Shuofeng Yuan / Vincent Kwok-Man Poon / Chris Chun-Sing Chan / Zhiwei Chen / Yang Luo / Marcus Cunningham / Alejandro Chavez / Michael T Yin / David S Perlin / Moriya Tsuji / Kwok-Yung Yuen / Peter D Kwong / Zizhang Sheng / Yaoxing Huang / Lawrence Shapiro / David D Ho / ![]() ![]() Abstract: The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related ...The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 143.4 KB | Display | ![]() |
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PDB format | ![]() | 107 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7sd5SC ![]() 7si2C ![]() 7ttxC ![]() 7ttyC S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 25860.971 Da / Num. of mol.: 1 / Fragment: receptor-binding domain (UNP residues 307-528) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||
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#2: Antibody | Mass: 24537.410 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||
#3: Antibody | Mass: 23257.518 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||
#4: Sugar | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.71 Å3/Da / Density % sol: 54.57 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop Details: 0.1 M sodium citrate, pH 5.2, 28% PEG4000, 0.2 M ammonium acetate |
-Data collection
Diffraction | Mean temperature: 110 K / Serial crystal experiment: N | ||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 27, 2021 | ||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97911 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 2.24→79.5 Å / Num. obs: 37400 / % possible obs: 98.6 % / Redundancy: 6.7 % / CC1/2: 0.99 / Rmerge(I) obs: 0.182 / Rpim(I) all: 0.083 / Rrim(I) all: 0.218 / Net I/σ(I): 6.4 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: ![]() |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB entry 7SD5 Resolution: 2.24→79.36 Å / SU ML: 0.35 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 29.18 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 131.46 Å2 / Biso mean: 56.8304 Å2 / Biso min: 28.07 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.24→79.36 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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