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- PDB-7k8o: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibo... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7k8o | |||||||||
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Title | Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C002 | |||||||||
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![]() | IMMUNE SYSTEM / Human Neutralizing Antibody / SARS-CoV-2 / Receptor Binding Domain / COVID-19 | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Jette, C.A. / Barnes, C.O. / Bjorkman, P.J. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 219.8 KB | Display | ![]() |
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PDB format | ![]() | 147.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 456.1 KB | Display | ![]() |
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Full document | ![]() | 457.8 KB | Display | |
Data in XML | ![]() | 17.9 KB | Display | |
Data in CIF | ![]() | 24.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7k8mC ![]() 7k8nC ![]() 7k8pC ![]() 7k8qC ![]() 7k8rC ![]() 7k8sC ![]() 7k8tC ![]() 7k8uC ![]() 7k8vC ![]() 7k8wC ![]() 7k8xC ![]() 7k8yC ![]() 7k8zC ![]() 7k90C ![]() 7bz5S 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: Antibody | Mass: 25370.459 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
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#2: Antibody | Mass: 23325.807 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#3: Chemical | ChemComp-GOL / #4: Chemical | ChemComp-SO4 / | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.3 Å3/Da / Density % sol: 62.75 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / Details: 0.2 M lithium sulfate monohydrate, 20% w/v PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 19, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.92→34.1 Å / Num. obs: 90103 / % possible obs: 99.24 % / Redundancy: 9.9 % / Biso Wilson estimate: 48.69 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.072 / Rpim(I) all: 0.024 / Net I/σ(I): 13 |
Reflection shell | Resolution: 1.92→1.99 Å / Rmerge(I) obs: 1.48 / Num. unique obs: 413 / CC1/2: 0.807 / Rpim(I) all: 0.334 / % possible all: 99.7 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB entry 7BZ5 Resolution: 1.95→34.1 Å / SU ML: 0.3116 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 35.5722 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: 72.14 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.95→34.1 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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