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Yorodumi- PDB-5aca: Structure-based energetics of protein interfaces guide Foot-and-M... -
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-Basic information
Entry | Database: PDB / ID: 5aca | ||||||
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Title | Structure-based energetics of protein interfaces guide Foot-and-Mouth disease virus vaccine design | ||||||
Components |
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Keywords | VIRUS / VACCINE / FOOT AND MOUTH DISEASE VIRUS / FMDV | ||||||
Function / homology | Function and homology information L-peptidase / icosahedral viral capsid / modulation by virus of host chromatin organization / RNA-protein covalent cross-linking / : / : / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane ...L-peptidase / icosahedral viral capsid / modulation by virus of host chromatin organization / RNA-protein covalent cross-linking / : / : / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / regulation of translation / clathrin-dependent endocytosis of virus by host cell / host cell cytoplasm / RNA helicase activity / viral protein processing / symbiont entry into host cell / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / RNA binding / ATP binding / cytoplasm Similarity search - Function | ||||||
Biological species | FOOT-AND-MOUTH DISEASE VIRUS - TYPE SAT 2 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
Authors | Kotecha, A. / Seago, J. / Scott, K. / Burman, A. / Loureiro, S. / Ren, J. / Porta, C. / Ginn, H.M. / Jackson, T. / Perez-Martin, E. ...Kotecha, A. / Seago, J. / Scott, K. / Burman, A. / Loureiro, S. / Ren, J. / Porta, C. / Ginn, H.M. / Jackson, T. / Perez-Martin, E. / Siebert, C.A. / Paul, G. / Huiskonen, J.T. / Jones, I.M. / Esnouf, R.M. / Fry, E.E. / Maree, F.F. / Charleston, B. / Stuart, D.I. | ||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2015 Title: Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design. Authors: Abhay Kotecha / Julian Seago / Katherine Scott / Alison Burman / Silvia Loureiro / Jingshan Ren / Claudine Porta / Helen M Ginn / Terry Jackson / Eva Perez-Martin / C Alistair Siebert / ...Authors: Abhay Kotecha / Julian Seago / Katherine Scott / Alison Burman / Silvia Loureiro / Jingshan Ren / Claudine Porta / Helen M Ginn / Terry Jackson / Eva Perez-Martin / C Alistair Siebert / Guntram Paul / Juha T Huiskonen / Ian M Jones / Robert M Esnouf / Elizabeth E Fry / Francois F Maree / Bryan Charleston / David I Stuart / Abstract: Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein ...Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids. | ||||||
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 | 5aca.cif.gz | 130.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5aca.ent.gz | 102.5 KB | Display | PDB format |
PDBx/mmJSON format | 5aca.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5aca_validation.pdf.gz | 1000.6 KB | Display | wwPDB validaton report |
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Full document | 5aca_full_validation.pdf.gz | 1010 KB | Display | |
Data in XML | 5aca_validation.xml.gz | 32 KB | Display | |
Data in CIF | 5aca_validation.cif.gz | 47.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ac/5aca ftp://data.pdbj.org/pub/pdb/validation_reports/ac/5aca | HTTPS FTP |
-Related structure data
Related structure data | 3130MC 3129C 5ac9C 5d8aC 5ddjC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 24160.209 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) FOOT-AND-MOUTH DISEASE VIRUS - TYPE SAT 2 Cell line (production host): BHK-21 / Production host: MESOCRICETUS AURATUS (golden hamster) / References: UniProt: Q1L764, UniProt: Q719N0*PLUS |
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#2: Protein | Mass: 23226.023 Da / Num. of mol.: 1 / Mutation: YES Source method: isolated from a genetically manipulated source Details: FMDV SAT2 SEROTYPE WITH A MUTATION AT VP2 S93Y Source: (gene. exp.) FOOT-AND-MOUTH DISEASE VIRUS - TYPE SAT 2 Cell line (production host): BHK-21 / Production host: MESOCRICETUS AURATUS (golden hamster) / References: UniProt: Q1L764, UniProt: Q719N0*PLUS |
#3: Protein | Mass: 24620.328 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) FOOT-AND-MOUTH DISEASE VIRUS - TYPE SAT 2 Cell line (production host): BHK-21 / Production host: MESOCRICETUS AURATUS (golden hamster) / References: UniProt: Q1L764 |
#4: Protein | Mass: 8836.233 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) FOOT-AND-MOUTH DISEASE VIRUS - TYPE SAT 2 Cell line (production host): BHK-21 / Production host: MESOCRICETUS AURATUS (golden hamster) / References: UniProt: Q1L764 |
Sequence details | VP2 S93Y |
-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: INACTIVATED FMDV SAT2 PARTICLE, STABILISED MUTANT / Type: VIRUS |
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Buffer solution | Name: 50MM HEPES PH 8.0, 200 MM NACL / pH: 8 / Details: 50MM HEPES PH 8.0, 200 MM NACL |
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: HOLEY CARBON |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE Details: VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 70, TEMPERATURE- 120, INSTRUMENT- FEI VITROBOT MARK IV, METHOD- BLOT FOR 3 SECONDS BEFORE PLUNGING, |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI F30 / Date: May 11, 2014 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 160000 X / Calibrated magnification: 37037 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm / Cs: 2 mm |
Image recording | Electron dose: 25 e/Å2 / Film or detector model: GATAN K2 (4k x 4k) |
Image scans | Num. digital images: 628 |
-Processing
EM software | Name: RELION / Category: 3D reconstruction | ||||||||||||
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CTF correction | Details: EACH PARTICLE | ||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||
3D reconstruction | Method: PROJECTION MATCHING / Resolution: 3.5 Å / Num. of particles: 8156 / Actual pixel size: 1.35 Å Magnification calibration: CROSS- -CORRELATION AGAINST ATOMIC MODEL Details: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3130. (DEPOSITION ID: 13687). Symmetry type: POINT | ||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL / Target criteria: Cross-correlation coefficient Details: METHOD--LOCAL CORRELATION FOLLOWED BY RIGIDBODY AND REAL SPACE REFINEMENT REFINEMENT PROTOCOL--CRYOEM | ||||||||||||
Refinement | Highest resolution: 3.5 Å | ||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 3.5 Å
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