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Yorodumi- PDB-8dnn: Crystal structure of neutralizing antibody 80 in complex with SAR... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dnn | ||||||
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Title | Crystal structure of neutralizing antibody 80 in complex with SARS-CoV-2 receptor binding domain | ||||||
Components |
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Keywords | IMMUNE SYSTEM/VIRAL PROTEIN / SARS-CoV-2 / ANTIBODY / VIRAL GLYCOPROTEIN / IMMUNE SYSTEM / IMMUNE SYSTEM-VIRAL PROTEIN 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 / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / 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 | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.12 Å | ||||||
Authors | Muthuraman, K. / Kucharska, I. / Ivanochko, D. / Julien, J.P. | ||||||
Funding support | United States, 1items
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Citation | Journal: Sci Transl Med / Year: 2023 Title: A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo. Authors: Clare Burn Aschner / Krithika Muthuraman / Iga Kucharska / Hong Cui / Katherine Prieto / Manoj S Nair / Maple Wang / Yaoxing Huang / Natasha Christie-Holmes / Betty Poon / Jessica Lam / ...Authors: Clare Burn Aschner / Krithika Muthuraman / Iga Kucharska / Hong Cui / Katherine Prieto / Manoj S Nair / Maple Wang / Yaoxing Huang / Natasha Christie-Holmes / Betty Poon / Jessica Lam / Azmiri Sultana / Robert Kozak / Samira Mubareka / John L Rubinstein / Edurne Rujas / Bebhinn Treanor / David D Ho / Arif Jetha / Jean-Philippe Julien / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments. MBs were shown to be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. In mice infected with SARS-CoV-2, a tri-specific MB targeting three regions within the SARS-CoV-2 receptor binding domain was protective at a 30-fold lower dose than a cocktail of the corresponding mAbs. Furthermore, we showed in vitro that mono-specific MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding mAbs lose their ability to neutralize potently, and that tri-specific MBs expanded the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dnn.cif.gz | 605.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dnn.ent.gz | 417.8 KB | Display | PDB format |
PDBx/mmJSON format | 8dnn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dnn_validation.pdf.gz | 879.4 KB | Display | wwPDB validaton report |
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Full document | 8dnn_full_validation.pdf.gz | 885.6 KB | Display | |
Data in XML | 8dnn_validation.xml.gz | 42.6 KB | Display | |
Data in CIF | 8dnn_validation.cif.gz | 58.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dn/8dnn ftp://data.pdbj.org/pub/pdb/validation_reports/dn/8dnn | HTTPS FTP |
-Related structure data
Related structure data | 7lm8S S: Starting model for refinement 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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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
NCS oper:
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-Components
#1: Protein | Mass: 25813.070 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 24198.188 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 24128.750 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Sugar | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3 Å3/Da / Density % sol: 58.94 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 0.2M di-ammonium tartarate, 20% (w/v) polyethylene glycol 3350 |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.033167 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 16, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.033167 Å / Relative weight: 1 |
Reflection | Resolution: 3.12→29.91 Å / Num. obs: 32395 / % possible obs: 99.79 % / Redundancy: 13.6 % / Biso Wilson estimate: 70.22 Å2 / CC1/2: 0.984 / Net I/σ(I): 6.03 |
Reflection shell | Resolution: 3.12→3.231 Å / Num. unique obs: 44891 / CC1/2: 0.615 / % possible all: 99.97 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7LM8 Resolution: 3.12→29.91 Å / SU ML: 0.4348 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 25.7772 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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: 63.85 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.12→29.91 Å
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Refine LS restraints |
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Refine LS restraints NCS |
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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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