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Yorodumi- PDB-7s0e: Structure of the SARS-CoV-2 S1 subunit in complex with antibody N... -
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-Basic information
Entry | Database: PDB / ID: 7s0e | ||||||
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Title | Structure of the SARS-CoV-2 S1 subunit in complex with antibody N-612-004 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / COVID-19 / Spike glycoprotein / mRNA Display / ANTIVIRAL PROTEIN / 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 / symbiont-mediated suppression of host innate immune response / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.9 Å | ||||||
Authors | Barnes, C.O. / Bjorkman, P.J. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2022 Title: Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display. Authors: Shiho Tanaka / C Anders Olson / Christopher O Barnes / Wendy Higashide / Marcos Gonzalez / Justin Taft / Ashley Richardson / Marta Martin-Fernandez / Dusan Bogunovic / Priyanthi N P ...Authors: Shiho Tanaka / C Anders Olson / Christopher O Barnes / Wendy Higashide / Marcos Gonzalez / Justin Taft / Ashley Richardson / Marta Martin-Fernandez / Dusan Bogunovic / Priyanthi N P Gnanapragasam / Pamela J Bjorkman / Patricia Spilman / Kayvan Niazi / Shahrooz Rabizadeh / Patrick Soon-Shiong / Abstract: The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or ...The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants. #1: Journal: bioRxiv / Year: 2021 Title: Rapid Identification of Neutralizing Antibodies against SARS-CoV-2 Variants by mRNA Display. Authors: Shiho Tanaka / C Anders Olson / Christopher O Barnes / Wendy Higashide / Marcos Gonzalez / Justin Taft / Ashley Richardson / Marta Martin-Fernandez / Dusan Bogunovic / Priyanthi N P ...Authors: Shiho Tanaka / C Anders Olson / Christopher O Barnes / Wendy Higashide / Marcos Gonzalez / Justin Taft / Ashley Richardson / Marta Martin-Fernandez / Dusan Bogunovic / Priyanthi N P Gnanapragasam / Pamela J Bjorkman / Patricia Spilman / Kayvan Niazi / Shahrooz Rabizadeh / Patrick Soon-Shiong Abstract: The increasing prevalence of SARS-CoV-2 variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly- ...The increasing prevalence of SARS-CoV-2 variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly-reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identified a set of antibodies against SARS-CoV-2 spike (S) proteins and characterized the structures of nAbs that recognized epitopes in the S1 subunit of the S glycoprotein. These structural studies revealed distinct binding modes for several antibodies, including targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interacts with angiotensin- converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. A potent ACE2-blocking nAb was further engineered to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is a promising approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7s0e.cif.gz | 206.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7s0e.ent.gz | 161.5 KB | Display | PDB format |
PDBx/mmJSON format | 7s0e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7s0e_validation.pdf.gz | 801.4 KB | Display | wwPDB validaton report |
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Full document | 7s0e_full_validation.pdf.gz | 829.6 KB | Display | |
Data in XML | 7s0e_validation.xml.gz | 45.8 KB | Display | |
Data in CIF | 7s0e_validation.cif.gz | 68.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/s0/7s0e ftp://data.pdbj.org/pub/pdb/validation_reports/s0/7s0e | HTTPS FTP |
-Related structure data
Related structure data | 24788MC 7s0bC 7s0cC 7s0dC M: map data used to model this data 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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-Components
#1: Protein | Mass: 141157.391 Da / Num. of mol.: 1 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 |
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#2: Antibody | Mass: 24349.105 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 23531.979 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Trimeric complex of SARS-CoV-2 spike glycoprotein bound to N-612-014 Fab fragments Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 |
-Processing
Software | Name: PHENIX / Version: 1.19.1_4122: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 107271 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
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