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- EMDB-30465: Cryo-EM structure of dengue virus serotype 2 in complex with the ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30465 | ||||||||||||
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Title | Cryo-EM structure of dengue virus serotype 2 in complex with the scFv fragment of the broadly neutralizing antibody EDE1 C10 | ||||||||||||
![]() | Dengue 2 NGC With ScFv C10 | ||||||||||||
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Function / homology | ![]() : / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / RNA helicase activity ...: / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / RNA helicase activity / 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 / serine-type endopeptidase activity / viral RNA genome replication / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / extracellular region / ATP binding / metal ion binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Zhang X / Sharma A / Duquerroy S / Zhou ZH / Rey FA | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses. Authors: Arvind Sharma / Xiaokang Zhang / Wanwisa Dejnirattisai / Xinghong Dai / Danyang Gong / Wiyada Wongwiwat / Stéphane Duquerroy / Alexander Rouvinski / Marie-Christine Vaney / Pablo Guardado- ...Authors: Arvind Sharma / Xiaokang Zhang / Wanwisa Dejnirattisai / Xinghong Dai / Danyang Gong / Wiyada Wongwiwat / Stéphane Duquerroy / Alexander Rouvinski / Marie-Christine Vaney / Pablo Guardado-Calvo / Ahmed Haouz / Patrick England / Ren Sun / Z Hong Zhou / Juthathip Mongkolsapaya / Gavin R Screaton / Felix A Rey / ![]() ![]() ![]() ![]() ![]() Abstract: The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative ...The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design. #1: ![]() Title: Structural basis of potent Zika-dengue virus antibody cross-neutralization. Authors: Barba-Spaeth G / Dejnirattisai W / Rouvinski A / Vaney MC / Medits I / Sharma A / Simon-Loriere E / Sakuntabhai A / Cao-Lormeau VM / Haouz A / England P / Stiasny K / Mongkolsapaya J / Heinz ...Authors: Barba-Spaeth G / Dejnirattisai W / Rouvinski A / Vaney MC / Medits I / Sharma A / Simon-Loriere E / Sakuntabhai A / Cao-Lormeau VM / Haouz A / England P / Stiasny K / Mongkolsapaya J / Heinz FX / Screaton GR / Rey FA | ||||||||||||
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 | ![]() | 925.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.7 KB 23.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 21.6 KB | Display | ![]() |
Images | ![]() | 110.9 KB | ||
Others | ![]() ![]() ![]() | 926.5 MB 155.5 MB 155.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 981.9 KB | Display | ![]() |
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Full document | ![]() | 981.5 KB | Display | |
Data in XML | ![]() | 29.7 KB | Display | |
Data in CIF | ![]() | 39.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7cthMC ![]() 7a3nC ![]() 7a3oC ![]() 7a3pC ![]() 7a3qC ![]() 7a3rC ![]() 7a3sC ![]() 7a3tC ![]() 7a3uC M: atomic model generated by this map 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
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Dengue 2 NGC With ScFv C10 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: unsharpen map
File | emd_30465_additional_1.map | ||||||||||||
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Annotation | unsharpen map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map A
File | emd_30465_half_map_1.map | ||||||||||||
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Annotation | Half Map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map B
File | emd_30465_half_map_2.map | ||||||||||||
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Annotation | Half Map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Dengue virus
Entire | Name: ![]() ![]() |
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Components |
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-Supramolecule #1: Dengue virus
Supramolecule | Name: Dengue virus / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #2-#4 / NCBI-ID: 12637 / Sci species name: Dengue virus / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: Yes / Virus empty: No |
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Host (natural) | Organism: ![]() |
-Macromolecule #1: Core protein
Macromolecule | Name: Core protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 54.351746 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT DSRCPTQGEP SLNEEQDKR FVCKHSMVDR GWGNGCGLFG KGGIVTCAMF TCKKNMKGKV VQPENLEYTI VITPHSGEEH AVGNDTGKHG K EIKITPQS ...String: MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT DSRCPTQGEP SLNEEQDKR FVCKHSMVDR GWGNGCGLFG KGGIVTCAMF TCKKNMKGKV VQPENLEYTI VITPHSGEEH AVGNDTGKHG K EIKITPQS SITEAELTGY GTVTMECSPR TGLDFNEMVL LQMENKAWLV HRQWFLDLPL PWLPGADTQG SNWIQKETLV TF KNPHAKK QDVVVLGSQE GAMHTALTGA TEIQMSSGNL LFTGHLKCRL RMDKLQLKGM SYSMCTGKFK VVKEIAETQH GTI VIRVQY EGDGSPCKIP FEIMDLEKRH VLGRLITVNP IVTEKDSPVN IEAEPPFGDS YIIIGVEPGQ LKLNWFKKGS SIGQ MIETT MRGAKRMAIL GDTAWDFGSL GGVFTSIGKA LHQVFGAIYG AAFSGVSWTM KILIGVIITW IGMNSRSTSL SVSLV LVGV VTLYLGVMVQ A |
-Macromolecule #2: Core protein
Macromolecule | Name: Core protein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO / EC number: flavivirin |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 8.345762 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SVALVPHVGM GLETRTETWM SSEGAWKHAQ RIETWILRHP GFTIMAAILA YTIGTTHFQR ALIFILLTAV APSMT |
-Macromolecule #3: Single Chain Variable Fragment
Macromolecule | Name: Single Chain Variable Fragment / type: protein_or_peptide / ID: 3 Details: heavy chain variable region of the broadly neutralizing antibody EDE1 C10 Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.679234 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAEVQLVESG AEVKKPGASV KVSCKASGYT FTSYAMHWVR QAPGQRLEWM GWINAGNGNT KYSQKFQDRV TITRDTSAST AYMELSSLR SEDTAIYYCA RDKVDDYGDY WFPTLWYFDY WGQGTLVTVS SGTGGSGGGG SGGGG |
-Macromolecule #4: Single Chain Variable Fragment
Macromolecule | Name: Single Chain Variable Fragment / type: protein_or_peptide / ID: 4 Details: light chain variable region of the broadly neutralizing antibody EDE1 C10 Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.632767 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SGGGASQSAL TQPASVSGSP GQSITISCTG TSSDVGGFNY VSWFQQHPGK APKLMLYDVT SRPSGVSSRF SGSKSGNTAS LTISGLQAE DEADYYCSSH TSRGTWVFGG GTKLTVLAAA DDDDKAGWSH PQFEKGGGSG GGSGGGSWSH PQFEK |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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 | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |