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- EMDB-29020: Structure of dengue virus (DENV2) in complex with prM12, an anti-... -
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Open data
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Basic information
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Title | Structure of dengue virus (DENV2) in complex with prM12, an anti-PrM monoclonal antibody | |||||||||
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![]() | Mus musculus != Dengue virus 2 Mus musculus
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![]() | DENV / flavivirus / prM antibody / prM12 / VIRUS-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / viral capsid / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / viral capsid / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / 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 / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 10.2 Å | |||||||||
![]() | Dowd AD / Sirohi D / Speer S / Mukherjee S / Govero J / Aleshnick M / Larman B / Sukupolvi-Petty S / Sevvana M / Miller AS ...Dowd AD / Sirohi D / Speer S / Mukherjee S / Govero J / Aleshnick M / Larman B / Sukupolvi-Petty S / Sevvana M / Miller AS / Klose T / Zheng A / Kielian M / Kuhn RJ / Diamond MS / Pierson TC | |||||||||
Funding support | ![]()
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![]() | ![]() Title: prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis. Authors: Kimberly A Dowd / Devika Sirohi / Scott D Speer / Laura A VanBlargan / Rita E Chen / Swati Mukherjee / Bradley M Whitener / Jennifer Govero / Maya Aleshnick / Bridget Larman / Soila ...Authors: Kimberly A Dowd / Devika Sirohi / Scott D Speer / Laura A VanBlargan / Rita E Chen / Swati Mukherjee / Bradley M Whitener / Jennifer Govero / Maya Aleshnick / Bridget Larman / Soila Sukupolvi-Petty / Madhumati Sevvana / Andrew S Miller / Thomas Klose / Aihua Zheng / Scott Koenig / Margaret Kielian / Richard J Kuhn / Michael S Diamond / Theodore C Pierson / ![]() Abstract: Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis ...Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state-dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact anti-prM mAbs resulted in an antibody-dependent enhancement of disease. However, protection against DENV-induced lethality was observed when the transferred mAbs were genetically modified to inhibit their ability to interact with Fcγ receptors. These data establish that in addition to mature forms of the virus, partially mature infectious prM virions can also contribute to pathogenesis during primary DENV infections. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 223.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.8 KB 21.8 KB | Display Display | ![]() |
Images | ![]() | 167.5 KB | ||
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() | 223.1 MB 223.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 890.1 KB | Display | ![]() |
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Full document | ![]() | 889.6 KB | Display | |
Data in XML | ![]() | 22 KB | Display | |
Data in CIF | ![]() | 26.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8fe3MC ![]() 8fe4C 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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Voxel size | X=Y=Z: 1.73 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_29020_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_29020_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Mus musculus
Entire | Name: ![]() ![]() |
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Components |
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-Supramolecule #1: Dengue virus 2
Supramolecule | Name: Dengue virus 2 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 11060 / Sci species name: Dengue virus 2 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: Yes / Virus empty: No |
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Virus shell | Shell ID: 1 / Diameter: 500.0 Å / T number (triangulation number): 3 |
-Macromolecule #1: prM12 Fab Heavy Chain
Macromolecule | Name: prM12 Fab Heavy Chain / type: protein_or_peptide / ID: 1 Details: The homology model of the prM12 variable heavy chain domain (1-124) was pieced together with the crystal structure of the constant heavy chain domain, derived from ZV-67, which belongs to ...Details: The homology model of the prM12 variable heavy chain domain (1-124) was pieced together with the crystal structure of the constant heavy chain domain, derived from ZV-67, which belongs to murine IgG2c isotype similar to prM12. Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.6165 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLQESGPE LVKPGTSVKM SCKASGYTFT DYNIHWVKQS HGKSLEWIGY INPNNGGNKY TQKFEGRATL TVGKSSSTAY MELRSLTSE DSAVYYCARS PMYFYYDGSY YFDYWGQGTS LSVSSAKTTA PSVYPLAPVC GGTTGSSVTL GCLVKGYFPE P VTLTWNSG ...String: EVQLQESGPE LVKPGTSVKM SCKASGYTFT DYNIHWVKQS HGKSLEWIGY INPNNGGNKY TQKFEGRATL TVGKSSSTAY MELRSLTSE DSAVYYCARS PMYFYYDGSY YFDYWGQGTS LSVSSAKTTA PSVYPLAPVC GGTTGSSVTL GCLVKGYFPE P VTLTWNSG SLSSGVHTFP ALLQSGLYTL SSSVTVTSNT WPSQTITCNV AHPASSTKVD KKIEPRVPI |
-Macromolecule #2: prM12 Fab Light Chain
Macromolecule | Name: prM12 Fab Light Chain / type: protein_or_peptide / ID: 2 Details: The homology model of the prM12 variable light chain domain (1-108) was pieced together with the crystal structure of the constant light chain domain, derived from ZV-67, which belongs to ...Details: The homology model of the prM12 variable light chain domain (1-108) was pieced together with the crystal structure of the constant light chain domain, derived from ZV-67, which belongs to murine IgG2c isotype similar to prM12. Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.530898 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIVLTQSPAS LAVSLGQRAT ISYRASKSVS TSGYSYMHWN QQKPGQPPRL LIYLVSNLES GVPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQHIRELT FGAAPSAAAR ADAAPTVSIF PPSSEQLTSG GASVVCFLNN FYPKDINVKW KIDGSERQNG V LNSWTDQD ...String: DIVLTQSPAS LAVSLGQRAT ISYRASKSVS TSGYSYMHWN QQKPGQPPRL LIYLVSNLES GVPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQHIRELT FGAAPSAAAR ADAAPTVSIF PPSSEQLTSG GASVVCFLNN FYPKDINVKW KIDGSERQNG V LNSWTDQD SKDSTYSMSS TLTLTKDEYE RHNSYTCEAT HKTSTSPIVK SFNRNEC |
-Macromolecule #3: Envelope protein E
Macromolecule | Name: Envelope protein E / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 43.892469 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MRCIGMSNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT ESRCPTQGEP SLNEEQDKR FVCKHSMVDR GWGNGCGLFG KGGIVTCAMF RCKKNMEGKV VQPENLEYTI VITPHSGEEH AVGNDTGKHG K EIKITPQS ...String: MRCIGMSNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT ESRCPTQGEP SLNEEQDKR FVCKHSMVDR GWGNGCGLFG KGGIVTCAMF RCKKNMEGKV 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 LKLNWFKK UniProtKB: Genome polyprotein |
-Macromolecule #4: prM protein
Macromolecule | Name: prM protein / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 9.261531 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: FHLTTRNGEP HMIVSRQEKG KSLLFKTEDG VNMCTLMAMD LGELCEDTIT YKCPLLRQNE PEDIDCWCNS TSTWVTYGTC T UniProtKB: Genome polyprotein |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 8 |
Grid | Model: PELCO Ultrathin Carbon with Lacey Carbon / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: LACEY |
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: SUPER-RESOLUTION / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 10.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: jspr / Number images used: 5881 |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: jspr |
Final angle assignment | Type: PROJECTION MATCHING |
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: RIGID BODY FIT | ||||||
Output model | ![]() PDB-8fe3: |