+Open data
-Basic information
Entry | Database: PDB / ID: 6zb5 | ||||||||||||||||||||||||
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Title | SARS CoV-2 Spike protein, Closed conformation, C3 symmetry | ||||||||||||||||||||||||
Components | Spike glycoprotein | ||||||||||||||||||||||||
Keywords | VIRAL PROTEIN / SARS-Cov2 / COVID / Linoleic Acid / Spike | ||||||||||||||||||||||||
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 / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.85 Å | ||||||||||||||||||||||||
Authors | Toelzer, C. / Gupta, K. / Yadav, S.K.N. / Burucu, U. / Schaffitzel, C. / Berger, I. | ||||||||||||||||||||||||
Funding support | United Kingdom, 7items
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Citation | Journal: Science / Year: 2020 Title: Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein. Authors: Christine Toelzer / Kapil Gupta / Sathish K N Yadav / Ufuk Borucu / Andrew D Davidson / Maia Kavanagh Williamson / Deborah K Shoemark / Frederic Garzoni / Oskar Staufer / Rachel Milligan / ...Authors: Christine Toelzer / Kapil Gupta / Sathish K N Yadav / Ufuk Borucu / Andrew D Davidson / Maia Kavanagh Williamson / Deborah K Shoemark / Frederic Garzoni / Oskar Staufer / Rachel Milligan / Julien Capin / Adrian J Mulholland / Joachim Spatz / Daniel Fitzgerald / Imre Berger / Christiane Schaffitzel / Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the ...Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms that drive high infectivity, broad tissue tropism, and severe pathology. Our 2.85-angstrom cryo-electron microscopy structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains tightly bind the essential free fatty acid linoleic acid (LA) in three composite binding pockets. A similar pocket also appears to be present in the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). LA binding stabilizes a locked S conformation, resulting in reduced angiotensin-converting enzyme 2 (ACE2) interaction in vitro In human cells, LA supplementation synergizes with the COVID-19 drug remdesivir, suppressing SARS-CoV-2 replication. Our structure directly links LA and S, setting the stage for intervention strategies that target LA binding by SARS-CoV-2. | ||||||||||||||||||||||||
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 | 6zb5.cif.gz | 551.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6zb5.ent.gz | 454.5 KB | Display | PDB format |
PDBx/mmJSON format | 6zb5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6zb5_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6zb5_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 6zb5_validation.xml.gz | 83.4 KB | Display | |
Data in CIF | 6zb5_validation.cif.gz | 133 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zb/6zb5 ftp://data.pdbj.org/pub/pdb/validation_reports/zb/6zb5 | HTTPS FTP |
-Related structure data
Related structure data | 11145MC 6zb4C 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: 139735.922 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 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2 #2: Polysaccharide | #3: Sugar | ChemComp-NAG / #4: Chemical | Has ligand of interest | Y | |
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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: SARS CoV-2 Spike protein, Closed conformation, C3 symmetry Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.54 MDa / Experimental value: NO |
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy imaging
Microscopy | Model: TFS TALOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: -2 nm / Nominal defocus min: -0.8 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: 11 sec. / Electron dose: 60.5 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3289 |
Image scans | Movie frames/image: 55 |
-Processing
Software | Name: PHENIX / Version: 1.17_3644: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 217815 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE | ||||||||||||||||||||||||
Refine LS restraints |
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