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Yorodumi- PDB-7rq6: Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutral... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rq6 | ||||||
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Title | Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing NTD-directed CV3-13 Fab isolated from convalescent individual | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / human non-neutralizing mAb / NTD-directed antibody / ADCC / novel NTD epitope / SARS-CoV-2 / spike / N-terminal domain / 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 | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.18 Å | ||||||
Authors | Chen, Y. / Pozharski, E. / Tolbert, W.D. / Pazgier, M. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2022 Title: A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. Authors: Guillaume Beaudoin-Bussières / Yaozong Chen / Irfan Ullah / Jérémie Prévost / William D Tolbert / Kelly Symmes / Shilei Ding / Mehdi Benlarbi / Shang Yu Gong / Alexandra Tauzin / Romain ...Authors: Guillaume Beaudoin-Bussières / Yaozong Chen / Irfan Ullah / Jérémie Prévost / William D Tolbert / Kelly Symmes / Shilei Ding / Mehdi Benlarbi / Shang Yu Gong / Alexandra Tauzin / Romain Gasser / Debashree Chatterjee / Dani Vézina / Guillaume Goyette / Jonathan Richard / Fei Zhou / Leonidas Stamatatos / Andrew T McGuire / Hughes Charest / Michel Roger / Edwin Pozharski / Priti Kumar / Walther Mothes / Pradeep D Uchil / Marzena Pazgier / Andrés Finzi / Abstract: Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can ...Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7rq6.cif.gz | 707.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rq6.ent.gz | 576.4 KB | Display | PDB format |
PDBx/mmJSON format | 7rq6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rq6_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7rq6_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7rq6_validation.xml.gz | 126.8 KB | Display | |
Data in CIF | 7rq6_validation.cif.gz | 189.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rq/7rq6 ftp://data.pdbj.org/pub/pdb/validation_reports/rq/7rq6 | HTTPS FTP |
-Related structure data
Related structure data | 24628MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 138022.984 Da / Num. of mol.: 3 / Mutation: F817P, A892P, A899P, A942P, K986P, V987P Source method: isolated from a genetically manipulated source Details: Prefusion-stabilized Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 24080.912 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) #3: Antibody | Mass: 23323.898 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) #4: Polysaccharide | 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 |
-Sample preparation
Component | Name: Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing, NTD-directed human antibody CV3-13 Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | |||||||||||||||
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Molecular weight | Value: 0.67 MDa / Experimental value: YES | |||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | |||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.504 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: SARS-CoV-2 HexaPro spike (GnT1- produced) was incubated with 15-fold excess of CV3-13 Fab overnight at 4oC before purification on a Superose 6 300/10 GL column (GE Healthcare). The complex ...Details: SARS-CoV-2 HexaPro spike (GnT1- produced) was incubated with 15-fold excess of CV3-13 Fab overnight at 4oC before purification on a Superose 6 300/10 GL column (GE Healthcare). The complex peak was harvested, concentrated to 0.50 mg/mL in the SEC buffer and immediately used for CryoEM grid preparation. | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 42.1531 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 2181 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
Particle selection | Num. of particles selected: 916236 | |||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | |||||||||||||||||||||
3D reconstruction | Resolution: 4.18 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 150882 / Symmetry type: POINT | |||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | |||||||||||||||||||||
Atomic model building |
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