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- EMDB-61507: Hepatitis E virus capsid protein E2s domain (genotype I) in compl... -
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Open data
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Basic information
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Title | Hepatitis E virus capsid protein E2s domain (genotype I) in complex with Fab C158 | |||||||||
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![]() | Hepatitis E virus / Capsid protein / E2s domain / Immune complex / C158 antibody / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() host cell endoplasmic reticulum / T=1 icosahedral viral capsid / host cell Golgi apparatus / host cell surface / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell / host cell nucleus / structural molecule activity / RNA binding / extracellular region Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.64 Å | |||||||||
![]() | Liu L / Zheng Q / Li S / Xia N | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Antibodies elicited by hepatitis E vaccination in humans confer cross-genus protection against rat hepatitis E virus. Authors: Zihao Chen / Liqin Liu / Jianwen Situ / Guanghui Li / Shaoqi Guo / Qi Lai / Shusheng Wu / Yanan Jiang / Jingyan Fan / Zimin Tang / Yu Li / Guiping Wen / Siling Wang / Dong Ying / Yonghao ...Authors: Zihao Chen / Liqin Liu / Jianwen Situ / Guanghui Li / Shaoqi Guo / Qi Lai / Shusheng Wu / Yanan Jiang / Jingyan Fan / Zimin Tang / Yu Li / Guiping Wen / Siling Wang / Dong Ying / Yonghao Liang / Stanley Siu-Fung Ho / Xiaodan Ma / James Yiu-Hung Tsoi / Estie Hon-Kiu Shun / Nicholas Foo-Siong Chew / Weihui Ma / Weiwei Mao / Tingting Li / Zhenqin Chen / Mujin Fang / Yingbin Wang / Hai Yu / Fa Zhang / Anna Jinxia Zhang / Shaowei Li / Ningshao Xia / Siddharth Sridhar / Qingbing Zheng / Zizheng Zheng / ![]() Abstract: BACKGROUND & AIMS: Paslahepevirus balayani (bHEV), also known as hepatitis E virus (HEV), encompasses eight genotypes, five of which infect humans. Rats are natural reservoirs of Rocahepevirus ratti ...BACKGROUND & AIMS: Paslahepevirus balayani (bHEV), also known as hepatitis E virus (HEV), encompasses eight genotypes, five of which infect humans. Rats are natural reservoirs of Rocahepevirus ratti genotype 1 (HEV-r-1; rat HEV; rHEV), which has recently been implicated in viral hepatitis. Despite the antigenic divergence between bHEV and rHEV, studies on shared protective antibodies remain rare. METHODS: Polyclonal and monoclonal antibody responses against bHEV and rHEV were analyzed using antibody enzyme-linked immunosorbent assays. The efficacy of six potent bHEV-elicited cross-reactive ...METHODS: Polyclonal and monoclonal antibody responses against bHEV and rHEV were analyzed using antibody enzyme-linked immunosorbent assays. The efficacy of six potent bHEV-elicited cross-reactive antibodies in preventing rHEV infection was evaluated via challenge assays in rats. Cryo-electron microscopy was performed to assess the structural basis for the differential protective efficacy of the six antibodies. The viral lysis ability of these antibodies was assessed by separately reacting purified HEV-b-1 and HEV-r-1 virions with each antibody. RESULTS: We determined that antibody responses to bHEV infection and vaccination possess limited cross-reactivity to rHEV and identified two cross-reactive antigenic sites within the E2s domain. ...RESULTS: We determined that antibody responses to bHEV infection and vaccination possess limited cross-reactivity to rHEV and identified two cross-reactive antigenic sites within the E2s domain. Structural analysis and animal challenge studies pinpointed potent cross-reactive antibodies targeting antigenic site 1, indicating its prophylactic efficacy against rHEV. Conversely, antibodies recognizing antigenic site 2 were found to facilitate viral lysis of bHEV but not rHEV. CONCLUSIONS: These findings underscore the importance of antigenic site 1 in the design of broad-spectrum vaccines and therapeutics to mitigate the impact of diverse HEV genotypes on human health. IMPACT AND IMPLICATIONS: Rat HEV (rHEV) spillover to humans represents an unprecedented threat. Significant antigenic differences between rHEV and bHEV (Paslahepevirus balayani) may exacerbate the ...IMPACT AND IMPLICATIONS: Rat HEV (rHEV) spillover to humans represents an unprecedented threat. Significant antigenic differences between rHEV and bHEV (Paslahepevirus balayani) may exacerbate the impact of viral hepatitis. Our study reveals that cross-reactive human antibodies can offer protection against rHEV infection. Cross-protective antibodies targeting antigenic site 1 can be used to guide the development of practical strategies for preventing rHEV infection. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 213.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.2 KB 18.2 KB | Display Display | ![]() |
Images | ![]() | 24.1 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 226.1 MB 226.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 740.6 KB | Display | ![]() |
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Full document | ![]() | 740.2 KB | Display | |
Data in XML | ![]() | 15.3 KB | Display | |
Data in CIF | ![]() | 18 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9jijMC ![]() 9jieC ![]() 9jifC ![]() 9jigC ![]() 9jiiC ![]() 9jikC ![]() 9jilC ![]() 9jimC ![]() 9jinC ![]() 9jioC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.65 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_61507_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_61507_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : HEV capsid protein E2s domain in complex with fab C158
Entire | Name: HEV capsid protein E2s domain in complex with fab C158 |
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Components |
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-Supramolecule #1: HEV capsid protein E2s domain in complex with fab C158
Supramolecule | Name: HEV capsid protein E2s domain in complex with fab C158 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: HEV E2s domain
Supramolecule | Name: HEV E2s domain / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: C158 Fab
Supramolecule | Name: C158 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Secreted protein ORF2
Macromolecule | Name: Secreted protein ORF2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 22.956402 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QLFYSRPVVS ANGEPTVKLY TSVENAQQDK GIAIPHDIDL GESRVVIQDY DNQHEQDRPT PSPAPSRPFS VLRANDVLWL SLTAAEYDQ STYGSSTGPV YVSDSVTLVN VATGAQAVAR SLDWTKVTLD GRPLSTIQQY SKTFFVLPLR GKLSFWEAGT T KAGYPYNY ...String: QLFYSRPVVS ANGEPTVKLY TSVENAQQDK GIAIPHDIDL GESRVVIQDY DNQHEQDRPT PSPAPSRPFS VLRANDVLWL SLTAAEYDQ STYGSSTGPV YVSDSVTLVN VATGAQAVAR SLDWTKVTLD GRPLSTIQQY SKTFFVLPLR GKLSFWEAGT T KAGYPYNY NTTASDQLLV ENAAGHRVAI STYTTSLGAG PVSISAVAVL APHSA UniProtKB: Pro-secreted protein ORF2 |
-Macromolecule #2: C158 Fab light chain
Macromolecule | Name: C158 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.661919 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSVLTQPPSV SAAPGQKVTI SCSGHSSNIA NNYVAWYQQL PGTAPKLLIY DNDKRPSGIP DRFSASKSGT SATLGITGLQ TGDEAHYYC ETWDSSLSLW VFGGGTMVTV L |
-Macromolecule #3: C158 Fab heavy chain
Macromolecule | Name: C158 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.630168 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQIVQSGAE VKKPGASVKV SCTASGYTFT RYGLVWVRQA PGQGLEWMGS INTGNANTIY SEKFQGRVSI TRDTSASTTY MELRSLRYE DTAVYFCARE RGGSVVEPAA HYMDVWGNGT TVSVTS |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |