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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-6855 | |||||||||
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Title | JEV-2H4 Fab complex | |||||||||
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Function / homology | ![]() symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell surface / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.6 Å | |||||||||
![]() | Qiu XD / Lei YF / Yang P / Gao Q / WANG N / Cao L / Yuan S / Wang XX / Xu ZK / Rao ZH | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies. Authors: Xiaodi Qiu / Yingfeng Lei / Pan Yang / Qiang Gao / Nan Wang / Lei Cao / Shuai Yuan / Xiaofang Huang / Yongqiang Deng / Wenyu Ma / Tianbing Ding / Fanglin Zhang / Xingan Wu / Junjie Hu / Shan- ...Authors: Xiaodi Qiu / Yingfeng Lei / Pan Yang / Qiang Gao / Nan Wang / Lei Cao / Shuai Yuan / Xiaofang Huang / Yongqiang Deng / Wenyu Ma / Tianbing Ding / Fanglin Zhang / Xingan Wu / Junjie Hu / Shan-Lu Liu / Chengfeng Qin / Xiangxi Wang / Zhikai Xu / Zihe Rao / ![]() ![]() Abstract: Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . JEV is the leading causative agent of ...Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . JEV is the leading causative agent of encephalitis, and is responsible for thousands of deaths each year in Asia. Humoral immunity is essential for protecting against flavivirus infections and passive immunization has been demonstrated to be effective in curing disease. Here, we demonstrate that JEV-specific monoclonal antibodies, 2F2 and 2H4, block attachment of the virus to its receptor and also prevent fusion of the virus. Neutralization of JEV by these antibodies is exceptionally potent and confers clear therapeutic benefit in mouse models. A single 20 μg dose of these antibodies resulted in 100% survival and complete clearance of JEV from the brains of mice. The 4.7 Å and 4.6 Å resolution cryo-electron microscopy structures of JEV-2F2-Fab and JEV-2H4-Fab complexes, together with the crystal structure of 2H4 Fab and our recent near-atomic structure of JEV , unveil the nature and location of epitopes targeted by the antibodies. Both 2F2 and 2H4 Fabs bind quaternary epitopes that span across three adjacent envelope proteins. Our results provide a structural and molecular basis for the application of 2F2 and 2H4 to treat JEV infection. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 1.3 GB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.6 KB 15.6 KB | Display Display | ![]() |
Images | ![]() | 220.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5ywpMUC ![]() 6854C ![]() 5ywfC ![]() 5ywoC M: atomic model generated by this map U: unfit; in different coordinate system*YM C: citing same article ( |
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Similar structure data |
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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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Voxel size | X=Y=Z: 1.38 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : JEV E protein with its mouse antibody H
Entire | Name: JEV E protein with its mouse antibody H |
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Components |
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-Supramolecule #1: JEV E protein with its mouse antibody H
Supramolecule | Name: JEV E protein with its mouse antibody H / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: JEV E protein
Macromolecule | Name: JEV E protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 53.508684 KDa |
Sequence | String: FNCLGMGNRD FIEGASGATW VDLVLEGDSC LTIMANDKPT LDVRMINIEA SQLAEVRSYC YHASVTDIST VARCPMTGEA HNEKRADSS YVCKQGFTDR GWGNGCGLFG KGSIDTCAKF SCTSKAIGRT IQPENIKYEV GIFVHGTTTS ENHGNYSAQV G ASQAAKFT ...String: FNCLGMGNRD FIEGASGATW VDLVLEGDSC LTIMANDKPT LDVRMINIEA SQLAEVRSYC YHASVTDIST VARCPMTGEA HNEKRADSS YVCKQGFTDR GWGNGCGLFG KGSIDTCAKF SCTSKAIGRT IQPENIKYEV GIFVHGTTTS ENHGNYSAQV G ASQAAKFT VTPNAPSITL KLGDYGEVTL DCEPRSGLNT EAFYVMTVGS KSFLVHREWF HDLALPWTPP SSTAWRNREL LM EFEEAHA TKQSVVALGS QEGGLHQALA GAIVVEYSSS VKLTSGHLKC RLKMDKLALK GTTYGMCTGK FSFAKNPADT GHG TVVIEL SYSGSDGPCK IPIVSVASLN DMTPVGRLVT VNPFVATSSA NSKVLVEMEP PFGDSYIVVG RGDKQINHHW HKAG STLGK AFLTTLKGAQ RLAALGDTAW DFGSIGGVFN SIGKAVHQVF GGAFRTLFGG MSWITQGLMG ALLLWMGVNA RDRSI ALAF LATGGVLLFL ATNVHA |
-Macromolecule #2: JEV M protein
Macromolecule | Name: JEV M protein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 8.250488 KDa |
Sequence | String: SVSVQTHGES SLVNKTETWL DSTKATRYLM KTENWIIRNP GYAFLAAVLG WMLGSNNGQR VVFTILLLLV APAY |
-Macromolecule #3: 2H4 light chain
Macromolecule | Name: 2H4 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.840303 KDa |
Sequence | String: DIVLTQSPAS LAVSLGQRAT ISCRASQSVS TSYMHWYQQK PGQPPRLLIY LVSNLESGVP SRFSGSGSGT DFTLNIHPVE AEDEATYYC QHIRELTRSE AGPSWLEIKR ADAAPTVSIF PPSSEQLTSG GASVVCFLNN FYPKDINVKW KIDGSERQNG V LNSWTDQD ...String: DIVLTQSPAS LAVSLGQRAT ISCRASQSVS TSYMHWYQQK PGQPPRLLIY LVSNLESGVP SRFSGSGSGT DFTLNIHPVE AEDEATYYC QHIRELTRSE AGPSWLEIKR ADAAPTVSIF PPSSEQLTSG GASVVCFLNN FYPKDINVKW KIDGSERQNG V LNSWTDQD SKDSTYSMSS TLTLTKDEYE RHNSYTCEAT HKTSTSPIVK SFNRNEC |
-Macromolecule #4: 2H4 heavy chain
Macromolecule | Name: 2H4 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.337305 KDa |
Sequence | String: QVQLMESGPE LKKPGETVKI SCKASGYTFT DYSMHWVKQA PGKGLKWMGW INTGTGEPTF AADFKGRFAF SLETSASTAY LQINNLKNE DTASYFCARG VGLYGVDYWG QGTSVTVSSP KTTPPSVYPL APVCGDTTGS MVTLGCLVKG YFPEPVTVTW N SGSLSSGV ...String: QVQLMESGPE LKKPGETVKI SCKASGYTFT DYSMHWVKQA PGKGLKWMGW INTGTGEPTF AADFKGRFAF SLETSASTAY LQINNLKNE DTASYFCARG VGLYGVDYWG QGTSVTVSSP KTTPPSVYPL APVCGDTTGS MVTLGCLVKG YFPEPVTVTW N SGSLSSGV HTFPAVLQSD LYTLSSSVTV PSSTWPSETV TCNVAHPASS TKVDKKIVPR |
-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 / Details: PBS |
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Grid | Material: COPPER / Mesh: 400 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: OTHER / Digitization - Dimensions - Width: 4000 pixel / Digitization - Dimensions - Height: 4000 pixel / Number real images: 2500 / Average exposure time: 8.0 sec. / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Calibrated defocus max: 3.0 µm / Calibrated defocus min: 1.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |