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- EMDB-6200: Cryo-electron microscopy of Enterovirus 71 (EV71) in complex with... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-6200 | |||||||||
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Title | Cryo-electron microscopy of Enterovirus 71 (EV71) in complex with Fab fragments of neutralizing antibody 22A12 | |||||||||
![]() | Reconstruction of EV71 procapsid in complex with Fab22A12 | |||||||||
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![]() | EV71 / picornavirus / Mab22A12 / antibody / Fab / neutralization / canyon / enterovirus / enterovirus 71 | |||||||||
Function / homology | ![]() : / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell ...: / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / induction by virus of host autophagy / 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 / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | |||||||||
Biological species | unidentified (others) / ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.8 Å | |||||||||
![]() | Shingler KL / Cifuente JO / Ashley RE / Makhov AM / Conway JF / Hafenstein S | |||||||||
![]() | ![]() Title: The enterovirus 71 procapsid binds neutralizing antibodies and rescues virus infection in vitro. Authors: Kristin L Shingler / Javier O Cifuente / Robert E Ashley / Alexander M Makhov / James F Conway / Susan Hafenstein / ![]() Abstract: Enterovirus 71 (EV71) is responsible for seasonal outbreaks of hand, foot, and mouth disease in the Asia-Pacific region. The virus has the capability to cause severe disease and death, especially in ...Enterovirus 71 (EV71) is responsible for seasonal outbreaks of hand, foot, and mouth disease in the Asia-Pacific region. The virus has the capability to cause severe disease and death, especially in young children. Although several vaccines are currently in clinical trials, no vaccines or therapeutics have been approved for use. Previous structural studies have revealed that two antigenically distinct capsid forms are produced in EV71-infected cells: an expanded empty capsid, sometimes called a procapsid, and the infectious virus. Specifically, an immunodominant epitope of EV71 that maps to the virus canyon is structurally different in the procapsid and virus. This structure-function study shows that the procapsid can sequester antibodies, thus enhancing EV71 infection in vitro. The results presented here suggest that, due to conformational differences between the EV71 procapsid and virus, the presence of the procapsid in natural virus infections should be considered in the future design of vaccines or therapeutics. IMPORTANCE: In a picornavirus infection, both an infectious and a noninfectious empty capsid, sometimes referred to as a procapsid, are produced. It was novel to discover that the procapsid form of ...IMPORTANCE: In a picornavirus infection, both an infectious and a noninfectious empty capsid, sometimes referred to as a procapsid, are produced. It was novel to discover that the procapsid form of EV71 was expanded and antigenically distinct from the infectious virus. Previously, it had been supposed that this empty capsid was an off-pathway dead end or at best served for storage of pentameric subunits, which was later shown to be unlikely. It remains unexplained why picornaviruses evolutionarily conserve the wasteful production of so much noninfectious capsid. Here, we demonstrate that the EV71 procapsid has different antigenic properties than the infectious virus. Thus, the procapsid has the capacity to sequester neutralizing antibody and protect the virus, promoting or restoring a successful infection in vitro. This important observation should be considered in the future design and development of vaccines and therapeutics. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 132.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.4 KB 10.4 KB | Display Display | ![]() |
Images | ![]() | 715.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3j91MC ![]() 3j93MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Reconstruction of EV71 procapsid in complex with Fab22A12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.27 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Fab fragment of 22A12 monoclonal antibody bound to Enterovirus 71...
Entire | Name: Fab fragment of 22A12 monoclonal antibody bound to Enterovirus 71 procapsid at the VP1 GH Loop |
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Components |
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-Supramolecule #1000: Fab fragment of 22A12 monoclonal antibody bound to Enterovirus 71...
Supramolecule | Name: Fab fragment of 22A12 monoclonal antibody bound to Enterovirus 71 procapsid at the VP1 GH Loop type: sample / ID: 1000 / Number unique components: 2 |
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-Supramolecule #1: Human enterovirus 71
Supramolecule | Name: Human enterovirus 71 / type: virus / ID: 1 / Name.synonym: EV71 Details: Virus procapsid was complexed with Fab fragments of neutralizing antibody 22A12. NCBI-ID: 39054 / Sci species name: Human enterovirus 71 / Sci species strain: 1095/Shiga / Database: NCBI / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: Yes / Syn species name: EV71 |
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Host (natural) | Organism: ![]() |
Virus shell | Shell ID: 1 / Diameter: 300 Å / T number (triangulation number): 3 |
-Macromolecule #1: neutralizing antibody 22A12 Fab
Macromolecule | Name: neutralizing antibody 22A12 Fab / type: protein_or_peptide / ID: 1 / Recombinant expression: No / Database: NCBI |
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Source (natural) | Organism: unidentified (others) |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.0 mg/mL |
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Buffer | pH: 7.5 / Details: 10 mM Tris, 200 mM NaCl, 50 mM MgCl2 |
Grid | Details: holey carbon Quantifoil EM grids |
Vitrification | Cryogen name: ETHANE-PROPANE MIXTURE / Instrument: FEI VITROBOT MARK III |
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Electron microscopy
Microscope | FEI TECNAI F20 |
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Date | Jul 15, 2011 |
Image recording | Category: FILM / Film or detector model: KODAK SO-163 FILM / Digitization - Scanner: NIKON SUPER COOLSCAN 9000 / Digitization - Sampling interval: 6.35 µm |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal magnification: 50000 |
Sample stage | Specimen holder model: GATAN LIQUID NITROGEN |
Experimental equipment | ![]() Model: Tecnai F20 / Image courtesy: FEI Company |
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Image processing
Details | Processing was completed with EMAN2 and AUTO3DEM. |
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CTF correction | Details: CTFFind3 |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 8.8 Å / Resolution method: OTHER / Software - Name: EMAN, EMAN2, AUTO3DEM, Chimera / Number images used: 15226 |
-Atomic model buiding 1
Initial model | PDB ID: |
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Software | Name: Situs |
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
Output model | ![]() PDB-3j91: ![]() PDB-3j93: |