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- PDB-7s0c: Structure of the SARS-CoV-2 S 6P trimer in complex with neutraliz... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7s0c | ||||||
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Title | Structure of the SARS-CoV-2 S 6P trimer in complex with neutralizing antibody N-612-017 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / COVID-19 / Spike glycoprotein / mRNA Display / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / 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 / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.25 Å | ||||||
![]() | Barnes, C.O. / Bjorkman, P.J. | ||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 670.5 KB | Display | ![]() |
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PDB format | ![]() | 553.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 114.2 KB | Display | |
Data in CIF | ![]() | 173.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 24786MC ![]() 7s0bC ![]() 7s0dC M: map data used to model this data 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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Components
#1: Protein | Mass: 141157.391 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Production host: ![]() #2: Antibody | Mass: 24381.281 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Antibody | Mass: 23483.916 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Trimeric complex of SARS-CoV-2 spike glycoprotein bound to N-612-014 Fab fragments Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
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 |
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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: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 108746 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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