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Yorodumi- PDB-7k8m: Structure of the SARS-CoV-2 receptor binding domain in complex wi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7k8m | |||||||||
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Title | Structure of the SARS-CoV-2 receptor binding domain in complex with the human neutralizing antibody Fab fragment, C102 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Human Neutralizing Antibody / SARS-CoV-2 / Receptor Binding Domain / COVID-19 / 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 / 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 | Homo sapiens (human) Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å | |||||||||
Authors | Jette, C.A. / Barnes, C.O. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nature / Year: 2020 Title: SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Authors: Christopher O Barnes / Claudia A Jette / Morgan E Abernathy / Kim-Marie A Dam / Shannon R Esswein / Harry B Gristick / Andrey G Malyutin / Naima G Sharaf / Kathryn E Huey-Tubman / Yu E Lee / ...Authors: Christopher O Barnes / Claudia A Jette / Morgan E Abernathy / Kim-Marie A Dam / Shannon R Esswein / Harry B Gristick / Andrey G Malyutin / Naima G Sharaf / Kathryn E Huey-Tubman / Yu E Lee / Davide F Robbiani / Michel C Nussenzweig / Anthony P West / Pamela J Bjorkman / Abstract: The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute ...The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein show promise therapeutically and are being evaluated clinically. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7k8m.cif.gz | 163.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7k8m.ent.gz | 102.2 KB | Display | PDB format |
PDBx/mmJSON format | 7k8m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7k8m_validation.pdf.gz | 461 KB | Display | wwPDB validaton report |
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Full document | 7k8m_full_validation.pdf.gz | 469.9 KB | Display | |
Data in XML | 7k8m_validation.xml.gz | 23.3 KB | Display | |
Data in CIF | 7k8m_validation.cif.gz | 31.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k8/7k8m ftp://data.pdbj.org/pub/pdb/validation_reports/k8/7k8m | HTTPS FTP |
-Related structure data
Related structure data | 7k8nC 7k8oC 7k8pC 7k8qC 7k8rC 7k8sC 7k8tC 7k8uC 7k8vC 7k8wC 7k8xC 7k8yC 7k8zC 7k90C 7bz5S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Antibody | Mass: 24622.443 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 23417.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
#3: Protein | Mass: 21152.633 Da / Num. of mol.: 1 / Fragment: receptor binding domain (UNP residues 331-517) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.07 Å3/Da / Density % sol: 59.98 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / Details: 0.2 M sodium citrate tribasic, 20% w/v PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 29, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 3.2→52.12 Å / Num. obs: 14722 / % possible obs: 99.7 % / Redundancy: 6.5 % / Biso Wilson estimate: 77.79 Å2 / CC1/2: 0.987 / Rmerge(I) obs: 0.16 / Rpim(I) all: 0.068 / Net I/σ(I): 6 |
Reflection shell | Resolution: 3.2→3.31 Å / Rmerge(I) obs: 0.492 / Num. unique obs: 1413 / CC1/2: 0.974 / Rpim(I) all: 0.232 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 7BZ5 Resolution: 3.2→52.12 Å / SU ML: 0.3955 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 22.0817 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: 73.34 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.2→52.12 Å
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Refine LS restraints |
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LS refinement shell |
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