Journal: Nat Commun / Year: 2020 Title: Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B. Authors: Kang Wang / Binyang Zheng / Li Zhang / Lunbiao Cui / Xuan Su / Qian Zhang / Zhenxi Guo / Yu Guo / Wei Zhang / Ling Zhu / Fengcai Zhu / Zihe Rao / Xiangxi Wang / Abstract: Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and ...Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.
History
Deposition
Jul 27, 2020
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Header (metadata) release
Aug 12, 2020
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Map release
Aug 12, 2020
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Update
Sep 16, 2020
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Current status
Sep 16, 2020
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
#20 - Aug 2001 Poliovirus and Rhinovirus similarity (22)
#200 - Aug 2016 Quasisymmetry in Icosahedral Viruses similarity (1)
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Map
File
Download / File: emd_30408.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel size
X=Y=Z: 1.32 Å
Density
Contour Level
By AUTHOR: 0.0275 / Movie #1: 0.0275
Minimum - Maximum
-0.066497274 - 0.12878916
Average (Standard dev.)
0.0013532102 (±0.009332559)
Symmetry
Space group: 1
Details
EMDB XML:
Map geometry
Axis order
X
Y
Z
Origin
-180
-180
-180
Dimensions
360
360
360
Spacing
360
360
360
Cell
A=B=C: 475.2 Å α=β=γ: 90.0 °
CCP4 map header:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.32
1.32
1.32
M x/y/z
360
360
360
origin x/y/z
0.000
0.000
0.000
length x/y/z
475.200
475.200
475.200
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
-163
-114
-126
NX/NY/NZ
210
124
170
MAP C/R/S
1
2
3
start NC/NR/NS
-180
-180
-180
NC/NR/NS
360
360
360
D min/max/mean
-0.066
0.129
0.001
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Supplemental data
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Sample components
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Entire : Echovirus E30 in complex with 6C5
Entire
Name: Echovirus E30 in complex with 6C5
Components
Complex: Echovirus E30 in complex with 6C5
Complex: E30
Protein or peptide: VP1
Protein or peptide: VP2
Protein or peptide: VP3
Complex: 6C5-Fab
Protein or peptide: Heavy chain
Protein or peptide: Light chain
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Supramolecule #1: Echovirus E30 in complex with 6C5
Supramolecule
Name: Echovirus E30 in complex with 6C5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: The complex is obtained by mixing E30 with 6C5
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Supramolecule #2: E30
Supramolecule
Name: E30 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3 Details: E30 particles purified from the cells inoculated with live E30
Source (natural)
Organism: Echovirus E30
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Supramolecule #3: 6C5-Fab
Supramolecule
Name: 6C5-Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4-#5 Details: Fab fragment generated by proteolytic cleavage of IgG antibody.
Source (natural)
Organism: Mus musculus (house mouse)
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Macromolecule #1: VP1
Macromolecule
Name: VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
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