|Entry||Database: EMDB / ID: EMD-0861|
|Title||The cryo-EM structure of HEV VLP in complex with Fab 3B6|
|Sample||Hepatitis E virus:|
|Function / homology|
Function and homology information
host cell surface / entry receptor-mediated virion attachment to host cell / host cell Golgi apparatus / T=1 icosahedral viral capsid / host cell endoplasmic reticulum / viral capsid / viral entry into host cell / host cell cytoplasm / structural molecule activity / RNA binding ...host cell surface / entry receptor-mediated virion attachment to host cell / host cell Golgi apparatus / T=1 icosahedral viral capsid / host cell endoplasmic reticulum / viral capsid / viral entry into host cell / host cell cytoplasm / structural molecule activity / RNA binding / extracellular region / identical protein binding / cytoplasm
Viral coat protein subunit / Hepatitis E virus structural protein 2
Protein ORF2 / Secreted protein ORF2
|Biological species||Hepatitis E virus|
|Method||single particle reconstruction / cryo EM / Resolution: 7.2 Å|
|Authors||Zheng Q / He M / Jiang J / Li S|
|Funding support|| China, 2 items |
|Citation||Journal: Proc Natl Acad Sci U S A / Year: 2019|
Title: Viral neutralization by antibody-imposed physical disruption.
Authors: Qingbing Zheng / Jie Jiang / Maozhou He / Zizheng Zheng / Hai Yu / Tingting Li / Wenhui Xue / Zimin Tang / Dong Ying / Zekai Li / Shuo Song / Xinlin Liu / Kaihang Wang / Zhiqing Zhang / ...Authors: Qingbing Zheng / Jie Jiang / Maozhou He / Zizheng Zheng / Hai Yu / Tingting Li / Wenhui Xue / Zimin Tang / Dong Ying / Zekai Li / Shuo Song / Xinlin Liu / Kaihang Wang / Zhiqing Zhang / Daning Wang / Yingbin Wang / Xiaodong Yan / Qinjian Zhao / Jun Zhang / Ying Gu / Shaowei Li / Ningshao Xia /
Abstract: In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical ...In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_0861.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.128 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Hepatitis E virus
|Entire||Name: Hepatitis E virus / Number of components: 1|
-Component #1: virus, Hepatitis E virus
|Virus||Name: Hepatitis E virusOrthohepevirus A / Class: VIRUS-LIKE PARTICLE / Empty: Yes / Enveloped: No / Isolate: OTHER|
|Species||Species: Hepatitis E virus|
|Source (engineered)||Expression System: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others)|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||Specimen conc.: 2 mg/mL / pH: 7.4|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 %|
-Electron microscopy imaging
Model: Tecnai F30 / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI F30|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 25 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: GATAN LIQUID NITROGEN|
|Camera||Detector: FEI FALCON II (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 1029|
|3D reconstruction||Resolution: 7.2 Å / Resolution method: FSC 0.143 CUT-OFF|
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