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Yorodumi- PDB-7kl9: Structure of the SARS-CoV-2 S 6P trimer in complex with the ACE2 ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7kl9 | ||||||
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Title | Structure of the SARS-CoV-2 S 6P trimer in complex with the ACE2 protein decoy, CTC-445.2 (State 4) | ||||||
Components |
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Keywords | ANTIVIRAL PROTEIN / SARS-CoV-2 / ACE2 decoy / mini-protein / inhibitor / COVID-19 | ||||||
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 / Attachment and Entry / membrane fusion / 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: 4.1 Å | ||||||
Authors | Barnes, C.O. / Bjorkman, P.J. | ||||||
Funding support | United States, 1items
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Citation | Journal: Science / Year: 2020 Title: De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2. Authors: Thomas W Linsky / Renan Vergara / Nuria Codina / Jorgen W Nelson / Matthew J Walker / Wen Su / Christopher O Barnes / Tien-Ying Hsiang / Katharina Esser-Nobis / Kevin Yu / Z Beau Reneer / ...Authors: Thomas W Linsky / Renan Vergara / Nuria Codina / Jorgen W Nelson / Matthew J Walker / Wen Su / Christopher O Barnes / Tien-Ying Hsiang / Katharina Esser-Nobis / Kevin Yu / Z Beau Reneer / Yixuan J Hou / Tanu Priya / Masaya Mitsumoto / Avery Pong / Uland Y Lau / Marsha L Mason / Jerry Chen / Alex Chen / Tania Berrocal / Hong Peng / Nicole S Clairmont / Javier Castellanos / Yu-Ru Lin / Anna Josephson-Day / Ralph S Baric / Deborah H Fuller / Carl D Walkey / Ted M Ross / Ryan Swanson / Pamela J Bjorkman / Michael Gale / Luis M Blancas-Mejia / Hui-Ling Yen / Daniel-Adriano Silva / Abstract: We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, ...We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge. | ||||||
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 | 7kl9.cif.gz | 597.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7kl9.ent.gz | 493.3 KB | Display | PDB format |
PDBx/mmJSON format | 7kl9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7kl9_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7kl9_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7kl9_validation.xml.gz | 115.2 KB | Display | |
Data in CIF | 7kl9_validation.cif.gz | 172.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kl/7kl9 ftp://data.pdbj.org/pub/pdb/validation_reports/kl/7kl9 | HTTPS FTP |
-Related structure data
Related structure data | 22916MC 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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-Components
#1: Protein | Mass: 139339.312 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Protein | Mass: 17216.268 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) #3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: 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
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Molecular weight | Value: .6 MDa / Experimental value: YES | ||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse sample | ||||||||||||||||||||||||
Specimen support | Details: 0.2 mA | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K / Details: 3s blot, 0 blot force |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA / Details: 3x3 beam tilt collection |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 45000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 3.6 sec. / Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2250 |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 420998 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26038 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
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