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- EMDB-8325: Beta-propiolactone treated coxsackievirus A16 empty procapsid -

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Entry
Database: EMDB / ID: 8325
TitleBeta-propiolactone treated coxsackievirus A16 empty procapsid
Map dataBeta-propiolactone treated coxsackievirus A16 empty procapsid
Samplecoxsackievirus A16 capsids:
virus
Function / homologyPeptidase 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) / T=pseudo3 icosahedral viral capsid / 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 / 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-triphosphatase / 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 / virion attachment to host cell / structural molecule activity / transcription, DNA-templated / RNA binding / membrane / ATP binding / Genome polyprotein
Function and homology information
SourceCOXSACKIEVIRUS A16
Methodsingle particle reconstruction / cryo EM / 6.5 Å resolution
AuthorsChen F / Yao C
CitationJournal: J. Virol. / Year: 2017
Title: Beta-Propiolactone Inactivation of Coxsackievirus A16 Induces Structural Alteration and Surface Modification of Viral Capsids.
Authors: Chen Fan / Xiaohua Ye / Zhiqiang Ku / Liangliang Kong / Qingwei Liu / Cong Xu / Yao Cong / Zhong Huang
Abstract: Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of action remain poorly understood. ...Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of action remain poorly understood. Here we present cryo-electron microscopy (cryo-EM) structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids at resolutions of 3.9 Å and 6.5 Å, respectively. Notably, both particles were found to adopt an expanded conformation resembling the 135S-like uncoating intermediate, with characteristic features including an opened 2-fold channel, the externalization of the N terminus of VP1 capsid protein, and the absence of pocket factor. However, major neutralizing epitopes are very well preserved on these particles. Further biochemical analyses revealed that BPL treatment impairs the abilities of CVA16 particles to bind to the attachment receptor heparan sulfate and to a conformation-dependent monoclonal antibody in a BPL dose-dependent manner, indicating that BPL is able to modify surface-exposed amino acid residues. Taken together, our results demonstrate that BPL treatment may induce alteration of the overall structure and surface properties of a nonenveloped viral capsid, thus revealing a novel mode of action of BPL. Beta-propiolactone (BPL) is commonly used as an inactivating reagent to produce viral vaccines. It is recognized that BPL inactivates viral infectivity through modification of viral nucleic acids. However, its effect on viral proteins remains largely unknown. Here, we present high-resolution cryo-EM structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids, which reveals an expanded overall conformation and characteristic features that are typical for the 135S-like uncoating intermediate. We further show that the BPL concentration affects the binding of inactivated CVA16 particles to their receptor/antibody. Thus, BPL treatment can alter the overall structure and surface properties of viral capsids, which may lead to antigenic and immunogenic variations. Our findings provide important information for future development of BPL-inactivated vaccines.
Validation ReportPDB-ID: 5tsk

SummaryFull report
PDB-ID: 5tsl

SummaryFull report
About validation report
DateDeposition: Aug 12, 2016 / Header (metadata) release: Oct 12, 2016 / Map release: Feb 1, 2017 / Last update: Jun 13, 2018

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.1
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.1
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: : PDB-5tsk, PDB-5tsl
  • Surface level: 0.1
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic models: PDB-5tsk
  • Imaged by Jmol
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  • Simplified surface model + fitted atomic model
  • Atomic models: PDB-5tsl
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

Fileemd_8325.map.gz (map file in CCP4 format, 256001 KB)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
400 pix
1.1 Å/pix.
= 440. Å
400 pix
1.1 Å/pix.
= 440. Å
400 pix
1.1 Å/pix.
= 440. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density
Contour Level:0.1 (by author), 0.1 (movie #1):
Minimum - Maximum-0.33193296 - 0.3592689
Average (Standard dev.)0.000030325617 (0.034534447)
Details

EMDB XML:

Space Group Number1
Map Geometry
Axis orderXYZ
Dimensions400400400
Origin-200.0-200.0-200.0
Limit199.0199.0199.0
Spacing400400400
CellA=B=C: 440.0 Å
α=β=γ: 90.0 deg.

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.11.11.1
M x/y/z400400400
origin x/y/z-220.000-220.000-220.000
length x/y/z440.000440.000440.000
α/β/γ90.00090.00090.000
start NX/NY/NZ
NX/NY/NZ
MAP C/R/S123
start NC/NR/NS-200-200-200
NC/NR/NS400400400
D min/max/mean-0.3280.3550.000

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Supplemental data

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Sample components

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Entire coxsackievirus A16 capsids

EntireName: coxsackievirus A16 capsids / Number of components: 1

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Component #1: virus, COXSACKIEVIRUS A16

VirusName: COXSACKIEVIRUS A16 / Class: VIRION / Empty: Yes / Enveloped: No / Isolate: SPECIES
MassTheoretical: 5 MDa
SpeciesSpecies: COXSACKIEVIRUS A16
Source (natural)Host Species: Homo sapiens (human)

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Experimental details

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Sample preparation

SpecimenSpecimen state: particle / Method: cryo EM
Sample solutionSpecimen conc.: 0.0032 mg/ml / pH: 7.6
VitrificationInstrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Temperature: 120 K / Humidity: 100 % / Details: blot for 2 seconds.

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 25 e/Å2 / Illumination mode: FLOOD BEAM
LensMagnification: 57000.0 X (nominal) / Cs: 0.007 mm / Imaging mode: BRIGHT FIELD / Defocus: 1500.0 - 2500.0 nm
Specimen HolderModel: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature: K ( 70.0 - 90.0 K)
CameraDetector: FEI FALCON II (4k x 4k)

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Image acquisition

Image acquisitionNumber of digital images: 1350
Details: Images were recorded on a Falcon II direct electron detector in the 18-frame movie mode

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Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: I (icosahedral) / Number of projections: 1642
3D reconstructionSoftware: jspr
CTF correction: CTF fitting was automatically performed using fitctf2.py program in jspr
Resolution: 6.5 Å / Resolution method: FSC 0.143 CUT-OFF

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Atomic model buiding

Modeling #1Refinement protocol: rigid body
Output model

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