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- EMDB-33003: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with... -

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Basic information

Entry
Database: EMDB / ID: EMD-33003
TitleCryo-EM structure of Coxsackievirus B1 A-particle in complex with nAb 9A3 (classified from CVB1 mature virion in complex with 8A10 and 9A3)
Map data
Sample
  • Complex: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with nAb 9A3 (classified from CVB1 mature virion in complex with 8A10 and 9A3)
Biological speciesCoxsackievirus B1
Methodsingle particle reconstruction / cryo EM / Resolution: 4.01 Å
AuthorsZheng Q / Zhu R / Sun H / Cheng T / Li S / Xia N
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Host Microbe / Year: 2022
Title: Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail.
Authors: Qingbing Zheng / Rui Zhu / Zhichao Yin / Longfa Xu / Hui Sun / Hai Yu / Yuanyuan Wu / Yichao Jiang / Qiongzi Huang / Yang Huang / Dongqing Zhang / Liqin Liu / Hongwei Yang / Maozhou He / ...Authors: Qingbing Zheng / Rui Zhu / Zhichao Yin / Longfa Xu / Hui Sun / Hai Yu / Yuanyuan Wu / Yichao Jiang / Qiongzi Huang / Yang Huang / Dongqing Zhang / Liqin Liu / Hongwei Yang / Maozhou He / Zhenhong Zhou / Yanan Jiang / Zhenqin Chen / Huan Zhao / Yuqiong Que / Zhibo Kong / Lizhi Zhou / Tingting Li / Jun Zhang / Wenxin Luo / Ying Gu / Tong Cheng / Shaowei Li / Ningshao Xia /
Abstract: Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. ...Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB.
History
DepositionMar 2, 2022-
Header (metadata) releaseSep 28, 2022-
Map releaseSep 28, 2022-
UpdateOct 5, 2022-
Current statusOct 5, 2022Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_33003.png

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Map

FileDownload / File: emd_33003.map.gz / Format: CCP4 / Size: 669.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.12 Å
Density
Contour LevelBy AUTHOR: 0.6
Minimum - Maximum-0.8552077 - 1.9761139
Average (Standard dev.)-0.0014742945 (±0.14012714)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions560560560
Spacing560560560
CellA=B=C: 627.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Cryo-EM structure of Coxsackievirus B1 A-particle in complex with...

EntireName: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with nAb 9A3 (classified from CVB1 mature virion in complex with 8A10 and 9A3)
Components
  • Complex: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with nAb 9A3 (classified from CVB1 mature virion in complex with 8A10 and 9A3)

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Supramolecule #1: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with...

SupramoleculeName: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with nAb 9A3 (classified from CVB1 mature virion in complex with 8A10 and 9A3)
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)Organism: Coxsackievirus B1

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TECNAI F30
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.9 µm / Nominal defocus min: 1.1 µm
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.01 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1055

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