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- PDB-3j93: Fitting of Fab into the cryoEM density map of EV71 procapsid in c... -
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Basic information
Entry | Database: PDB / ID: 3j93 | ||||||
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Title | Fitting of Fab into the cryoEM density map of EV71 procapsid in complex with Fab22A12 | ||||||
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![]() | IMMUNE SYSTEM / Fab / EV71 / Fab22A12 | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 8.8 Å | ||||||
![]() | Shingler, K.L. / Cifuente, J.O. / Ashley, R.E. / Makhov, A.M. / Conway, J.F. / 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 | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 88.9 KB | Display | ![]() |
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PDB format | ![]() | 71.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 738.6 KB | Display | ![]() |
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Full document | ![]() | 749.6 KB | Display | |
Data in XML | ![]() | 22.2 KB | Display | |
Data in CIF | ![]() | 30.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6200MC ![]() 3j91C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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3 | ![]()
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
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Components
#1: Antibody | Mass: 23261.770 Da / Num. of mol.: 1 / Fragment: Fab / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: Antibody | Mass: 23349.105 Da / Num. of mol.: 1 / Fragment: Fab / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component |
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Details of virus | Empty: YES / Enveloped: NO / Host category: VERTEBRATES / Isolate: STRAIN / Type: VIRION | ||||||||||||||||
Natural host | Organism: Homo sapiens / Strain: HeLa | ||||||||||||||||
Buffer solution | Name: 10 mM Tris, 200 mM NaCl, 50 mM MgCl2 / pH: 7.5 / Details: 10 mM Tris, 200 mM NaCl, 50 mM MgCl2 | ||||||||||||||||
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Specimen support | Details: holey carbon Quantifoil EM grids | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE Details: Plunged into ethane-propane mixture (FEI VITROBOT MARK III) |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Tecnai F20 / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI F20 / Date: Jul 15, 2011 |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 50000 X / Cs: 2 mm / Camera length: 0 mm |
Specimen holder | Specimen holder model: GATAN LIQUID NITROGEN |
Image recording | Film or detector model: KODAK SO-163 FILM |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
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Processing
EM software |
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CTF correction | Details: CTFFind3 | ||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||
3D reconstruction | Method: Single Particle Reconstruction / Resolution: 8.8 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 15226 / Nominal pixel size: 1.27 Å / Actual pixel size: 1.27 Å Details: (Single particle details: Processing was completed with EMAN2 and AUTO3DEM) (Single particle--Applied symmetry: I) Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 3GK8 | ||||||||||||||||||||||||
Refinement step | Cycle: LAST
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