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Yorodumi- PDB-8vao: Simulation-driven design of prefusion stabilized SARS-CoV-2 spike... -
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-Basic information
Entry | Database: PDB / ID: 8vao | ||||||
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Title | Simulation-driven design of prefusion stabilized SARS-CoV-2 spike S2 antigen | ||||||
Components | Spike protein S2 | ||||||
Keywords | VIRAL PROTEIN / SARS-CoV-2 / spike protein / viral fusion / viral glycoprotein | ||||||
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 / 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 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Zhou, L. / McLellan, J.S. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens. Authors: Xandra Nuqui / Lorenzo Casalino / Ling Zhou / Mohamed Shehata / Albert Wang / Alexandra L Tse / Anupam A Ojha / Fiona L Kearns / Mia A Rosenfeld / Emily Happy Miller / Cory M Acreman / Surl- ...Authors: Xandra Nuqui / Lorenzo Casalino / Ling Zhou / Mohamed Shehata / Albert Wang / Alexandra L Tse / Anupam A Ojha / Fiona L Kearns / Mia A Rosenfeld / Emily Happy Miller / Cory M Acreman / Surl-Hee Ahn / Kartik Chandran / Jason S McLellan / Rommie E Amaro / Abstract: The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the ...The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2's usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimer's opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
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PDBx/mmCIF format | 8vao.cif.gz | 475.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8vao.ent.gz | 398.3 KB | Display | PDB format |
PDBx/mmJSON format | 8vao.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8vao_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8vao_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8vao_validation.xml.gz | 52.8 KB | Display | |
Data in CIF | 8vao_validation.cif.gz | 77.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/va/8vao ftp://data.pdbj.org/pub/pdb/validation_reports/va/8vao | HTTPS FTP |
-Related structure data
Related structure data | 43097MC 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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1 |
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-Components
#1: Protein | Mass: 56323.484 Da / Num. of mol.: 3 Mutation: S704C, K790C, F817P, A892P, A899P, A942P, Q957E, K986P, V987P, V991W, T998W Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): Freestyle 293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: 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: SARS-CoV-2 spike S2 trimer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Freestyle 293F |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 249447 / Symmetry type: POINT | ||||||||||||||||||||||||
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