+Open data
-Basic information
Entry | Database: PDB / ID: 6x2a | |||||||||||||||
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Title | SARS-CoV-2 u1S2q 1-RBD Up Spike Protein Trimer | |||||||||||||||
Components | Spike glycoprotein | |||||||||||||||
Keywords | VIRAL PROTEIN / Trimer | |||||||||||||||
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 / symbiont-mediated suppression of host innate immune response / 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: 3.3 Å | |||||||||||||||
Authors | Henderson, R. / Acharya, P. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nat Struct Mol Biol / Year: 2020 Title: Controlling the SARS-CoV-2 spike glycoprotein conformation. Authors: Rory Henderson / Robert J Edwards / Katayoun Mansouri / Katarzyna Janowska / Victoria Stalls / Sophie M C Gobeil / Megan Kopp / Dapeng Li / Rob Parks / Allen L Hsu / Mario J Borgnia / Barton ...Authors: Rory Henderson / Robert J Edwards / Katayoun Mansouri / Katarzyna Janowska / Victoria Stalls / Sophie M C Gobeil / Megan Kopp / Dapeng Li / Rob Parks / Allen L Hsu / Mario J Borgnia / Barton F Haynes / Priyamvada Acharya / Abstract: The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The ...The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications. #1: Journal: bioRxiv / Year: 2020 Title: Controlling the SARS-CoV-2 Spike Glycoprotein Conformation. Authors: Rory Henderson / Robert J Edwards / Katayoun Mansouri / Katarzyna Janowska / Victoria Stalls / Sophie Gobeil / Megan Kopp / Allen Hsu / Mario Borgnia / Rob Parks / Barton F Haynes / Priyamvada Acharya / Abstract: The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S- ...The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. We found that despite overall similarity in domain organization, different β-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs 'down' position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs 'up' configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications. | |||||||||||||||
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 | 6x2a.cif.gz | 515.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6x2a.ent.gz | 398 KB | Display | PDB format |
PDBx/mmJSON format | 6x2a.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6x2a_validation.pdf.gz | 881.8 KB | Display | wwPDB validaton report |
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Full document | 6x2a_full_validation.pdf.gz | 891.9 KB | Display | |
Data in XML | 6x2a_validation.xml.gz | 68.9 KB | Display | |
Data in CIF | 6x2a_validation.cif.gz | 108.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x2/6x2a ftp://data.pdbj.org/pub/pdb/validation_reports/x2/6x2a | HTTPS FTP |
-Related structure data
Related structure data | 21999MC 6x29C 6x2bC 6x2cC 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: 140790.453 Da / Num. of mol.: 3 / Fragment: ectodomain (UNP residues 16-1208) / Mutation: F855Y+N856I+A570L+T572I 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 Has protein modification | 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: Severe acute respiratory syndrome coronavirus 2 / Type: VIRUS / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Homo sapiens (human) |
Details of virus | Empty: NO / Enveloped: YES / Isolate: OTHER / Type: VIRION |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 66.82 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 255013 / Symmetry type: POINT |