|Entry||Database: PDB / ID: 3j91|
|Title||Cryo-electron microscopy of Enterovirus 71 (EV71) procapsid in complex with Fab fragments of neutralizing antibody 22A12|
|Keywords||VIRUS / EV71 / picornavirus / Mab22A12 / antibody / Fab / neutralization / canyon|
|Function / homology||Peptidase C3, picornavirus core protein 2A / P-loop containing nucleoside triphosphate hydrolase / Helicase, superfamily 3, single-stranded RNA virus / Peptidase S1, PA clan / RNA-directed RNA polymerase, catalytic domain / AAA+ ATPase domain / Picornavirus coat protein VP4 / Picornavirus 2B protein / Picornavirus capsid / RNA-directed RNA polymerase, C-terminal domain ...Peptidase C3, picornavirus core protein 2A / P-loop containing nucleoside triphosphate hydrolase / Helicase, superfamily 3, single-stranded RNA virus / Peptidase S1, PA clan / RNA-directed RNA polymerase, catalytic domain / AAA+ ATPase domain / Picornavirus coat protein VP4 / Picornavirus 2B protein / Picornavirus capsid / RNA-directed RNA polymerase, C-terminal domain / Helicase, superfamily 3, single-stranded DNA/RNA virus / Peptidase C3A/C3B, picornaviral / Viral coat protein subunit / Picornavirus/Calicivirus coat protein / Poliovirus core protein 3a, soluble domain / picornavirus capsid protein / RNA dependent RNA polymerase / Superfamily 3 helicase of positive ssRNA viruses domain profile. / RdRp of positive ssRNA viruses catalytic domain profile. / Poliovirus 3A protein like / Picornavirus coat protein (VP4) / Picornavirus 2B protein / Picornavirus core protein 2A / RNA helicase / Poliovirus 3A protein-like / 3C cysteine protease (picornain 3C) / picornain 2A / pore-mediated entry of viral genome into host cell / suppression by virus of host mRNA export from nucleus / suppression by virus of host RIG-I activity / picornain 3C / T=pseudo3 icosahedral viral capsid / endocytosis involved in viral entry into host cell / RNA-protein covalent cross-linking / host cell cytoplasmic vesicle membrane / pore formation by virus in membrane of host cell / integral to membrane of host cell / RNA helicase activity / nucleoside-triphosphate phosphatase / RNA-directed RNA polymerase / induction by virus of host autophagy / suppression by virus of host gene expression / ion channel activity / protein complex oligomerization / viral RNA genome replication / RNA-directed 5'-3' RNA polymerase activity / cysteine-type endopeptidase activity / transcription, DNA-templated / virion attachment to host cell / structural molecule activity / RNA binding / membrane / ATP binding / Genome polyprotein|
Function and homology information
|Specimen source||Enterovirus A71|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 8.8 Å resolution|
|Authors||Shingler, K.L. / Cifuente, J.O. / Ashley, R.E. / Makhov, A.M. / Conway, J.F. / Hafenstein, S.|
|Citation||Journal: J. Virol. / Year: 2015|
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 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.
SummaryFull reportAbout validation report
|Date||Deposition: Nov 24, 2014 / Release: Dec 10, 2014|
|Structure viewer||Molecule: |
Downloads & links
0: VP0x 60
0: VP0x 5
0: VP0x 6
|#1: Protein/peptide|| |
Mass: 35223.246 Da / Num. of mol.: 1 / Fragment: UNP residues 1-323 / Source: (natural) Enterovirus A71 / Strain: 1095/Shiga / References: UniProt: E5RPG0
|#2: Protein/peptide|| |
Mass: 32646.758 Da / Num. of mol.: 1 / Fragment: UNP residues 566-682 / Source: (natural) Enterovirus A71 / Strain: 1095/Shiga / References: UniProt: E5RPG0
|#3: Protein/peptide|| |
Mass: 26466.227 Da / Num. of mol.: 1 / Fragment: UNP residues 324-565 / Source: (natural) Enterovirus A71 / Strain: 1095/Shiga / References: UniProt: E5RPG0
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Details of virus||Empty: YES / Enveloped: NO / Virus host category: VERTEBRATES / Virus isolate: STRAIN / Virus type: VIRION|
|Natural host||Organism: Homo sapiens / Strain: HeLa|
|Buffer solution||Name: 10 mM Tris, 200 mM NaCl, 50 mM MgCl2 / Details: 10 mM Tris, 200 mM NaCl, 50 mM MgCl2 / pH: 7.5|
|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)
-Electron microscopy imaging
Model: Tecnai F20 / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TECNAI F20 / Date: Jul 15, 2011|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 50000 / 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||Diffraction protocol: SINGLE WAVELENGTH / Monochromatic or laue m l: M / Scattering type: x-ray|
|Radiation wavelength||Relative weight: 1|
|CTF correction||Details: CTFFind3|
|Symmetry||Point symmetry: I|
|3D reconstruction||Method: Single Particle ReconstructionSingle particle analysis|
Resolution: 8.8 Å / Resolution method: FSC 0.5 CUT-OFF / Number of particles: 15226 / Nominal pixel size: 1.27 / Actual pixel size: 1.27
Details: (Single particle details: Processing was completed with EMAN2 and AUTO3DEM) (Single particle--Applied symmetry: I)
Symmetry type: POINT
|Atomic model building||Details: REFINEMENT PROTOCOL--rigid body / Ref protocol: RIGID BODY FIT / Ref space: REAL|
|Atomic model building||PDB-ID: 4GMP|
|Number of atoms included #LAST||Protein: 5395 / Nucleic acid: 0 / Ligand: 0 / Solvent: 0 / Total: 5395|
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