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- EMDB-61511: Rat hepatitis E virus capsid protein E2s domain in complex with Fab H4 -
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Open data
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Basic information
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Title | Rat hepatitis E virus capsid protein E2s domain in complex with Fab H4 | |||||||||
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![]() | Hepatitis E virus / Capsid protein / E2s domain / Immune complex / H4 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 / structural molecule activity / RNA binding / extracellular region Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.56 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-EM 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. ...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: rHEV spillover to humans represents an unprecedented threat. Significant antigenic differences between rHEV and bHEV 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 inform 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 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
Images | ![]() | 34.3 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 226.4 MB 226.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 788.3 KB | Display | ![]() |
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Full document | ![]() | 787.9 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 | ![]() 9jinMC ![]() 9jieC ![]() 9jifC ![]() 9jigC ![]() 9jiiC ![]() 9jijC ![]() 9jikC ![]() 9jilC ![]() 9jimC ![]() 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: #2
File | emd_61511_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_61511_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Rat HEV capsid protein E2s domain in complex with Fab H4
Entire | Name: Rat HEV capsid protein E2s domain in complex with Fab H4 |
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Components |
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-Supramolecule #1: Rat HEV capsid protein E2s domain in complex with Fab H4
Supramolecule | Name: Rat HEV capsid protein E2s domain in complex with Fab H4 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: Rat HEV E2s domain
Supramolecule | Name: Rat HEV E2s domain / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: H4 Fab
Supramolecule | Name: H4 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Pro-secreted protein ORF2
Macromolecule | Name: Pro-secreted protein ORF2 / type: protein_or_peptide / ID: 1 Details: Sequence reference for source organism Rocahepevirus ratti is not available in UniProt at the time of biocuration. Current sequence reference is from UniProt id A0A3G1TVH2. Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 16.533393 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: PARPITNWRS GDVVWVTLPS AEYAQSQSAM GSHPAYWSEE ATIINVATGQ RAAVSSIKWD QVTLNGKALH KETHSGLVYY QLPLMGKIN FWQQGTTKAG YTYNYNTTDS DSLWVWWDGG SKAYLYISTY TTMLGAGPVN ITGLGAVGPN PV UniProtKB: Pro-secreted protein ORF2 |
-Macromolecule #2: H4 Fab heavy chain
Macromolecule | Name: H4 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.244089 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGASVKV ACKASGYNFI HYYLHWVRQA PGQGLEWMGI INPSVGRTTY AQKFQGRVTM TRDTSTSTVY MELSSLRSE DTAVYYCARD VGGMTYCGDE CFPPRGWFDP WGQGTLVTV |
-Macromolecule #3: H4 Fab light chain
Macromolecule | Name: H4 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.06225 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPQVPVSLSA SVGDRVTITC QASQDIGNYL TWSQQKPGKA PKLLIYDASN LQTGVPSRFS GSGSGTYFTL TISSLQPEDI ATYYCQQYD NVPITFGGGT EVEI |
-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 |