+Open data
-Basic information
Entry | Database: PDB / ID: 7sn1 | ||||||
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Title | Structure of human SARS-CoV-2 neutralizing antibody C1C-A3 Fab | ||||||
Components |
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Keywords | IMMUNE SYSTEM / COVID-19 / SARS-CoV-2 / neutralizing antibody / neutralization escape | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.467 Å | ||||||
Authors | Pan, J. / Abraham, J. / Clark, S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Science / Year: 2022 Title: Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. Authors: Katherine G Nabel / Sarah A Clark / Sundaresh Shankar / Junhua Pan / Lars E Clark / Pan Yang / Adrian Coscia / Lindsay G A McKay / Haley H Varnum / Vesna Brusic / Nicole V Tolan / Guohai ...Authors: Katherine G Nabel / Sarah A Clark / Sundaresh Shankar / Junhua Pan / Lars E Clark / Pan Yang / Adrian Coscia / Lindsay G A McKay / Haley H Varnum / Vesna Brusic / Nicole V Tolan / Guohai Zhou / Michaël Desjardins / Sarah E Turbett / Sanjat Kanjilal / Amy C Sherman / Anand Dighe / Regina C LaRocque / Edward T Ryan / Casey Tylek / Joel F Cohen-Solal / Anhdao T Darcy / Davide Tavella / Anca Clabbers / Yao Fan / Anthony Griffiths / Ivan R Correia / Jane Seagal / Lindsey R Baden / Richelle C Charles / Jonathan Abraham / Abstract: Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we ...Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7sn1.cif.gz | 267.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sn1.ent.gz | 218.5 KB | Display | PDB format |
PDBx/mmJSON format | 7sn1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7sn1_validation.pdf.gz | 433.7 KB | Display | wwPDB validaton report |
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Full document | 7sn1_full_validation.pdf.gz | 434.9 KB | Display | |
Data in XML | 7sn1_validation.xml.gz | 23.2 KB | Display | |
Data in CIF | 7sn1_validation.cif.gz | 36.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sn/7sn1 ftp://data.pdbj.org/pub/pdb/validation_reports/sn/7sn1 | HTTPS FTP |
-Related structure data
Related structure data | 7sn0C 7sn2C 7sn3C 4dgvS 4ptuS 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: 27022.607 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: mature antibody (after somatic hypermutation) from germline gene IGHV3-33 Source: (gene. exp.) Homo sapiens (human) / Gene: IGHV3-33 / Plasmid: pVRC8400 Cell line (production host): HEK-293 (Thermo Fisher Expi293F) Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 25896.107 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: mature antibody (after somatic hypermutation) from germline gene IGKV3-11 Source: (gene. exp.) Homo sapiens (human) / Gene: IGKV3-11 / Plasmid: pVRC8400 Cell line (production host): HEK-293T (Thermo Fisher Expi293F) Production host: Homo sapiens (human) |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.03 Å3/Da / Density % sol: 39.39 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.9 Details: 18% PEG 8000, 0.02 M Magnesium chloride hexahydrate, and 0.1 M Tris pH 8.9 PH range: 7.5-8.9 |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.97918 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 22, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 1.467→200 Å / Num. obs: 137494 / % possible obs: 98.9 % / Redundancy: 2.19 % / Biso Wilson estimate: 27.486 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.059 / Rrim(I) all: 0.077 / Χ2: 0.89 / Net I/σ(I): 8.45 |
Reflection shell | Resolution: 1.467→1.56 Å / Redundancy: 2.17 % / Rmerge(I) obs: 0.934 / Mean I/σ(I) obs: 1.14 / Num. unique obs: 21177 / CC1/2: 0.336 / Rrim(I) all: 1.217 / Χ2: 0.73 / % possible all: 96.2 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: composite model generated from heavy and light chains from PDB codes 4DGV and 4PTU, respectively. Resolution: 1.467→55.64 Å / Rfactor Rfree error: 26.11 / Cross valid method: THROUGHOUT / σ(F): 0
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Refinement step | Cycle: LAST / Resolution: 1.467→55.64 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.47→1.48 Å
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Refinement TLS params. | Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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