[English] 日本語
Yorodumi- EMDB-29020: Structure of dengue virus (DENV2) in complex with prM12, an anti-... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29020 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of dengue virus (DENV2) in complex with prM12, an anti-PrM monoclonal antibody | |||||||||
Map data | ||||||||||
Sample | Mus musculus != Dengue virus 2 Mus musculus
| |||||||||
Keywords | DENV / flavivirus / prM antibody / prM12 / VIRUS-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information 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 / viral capsid / double-stranded RNA binding / 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 / viral capsid / double-stranded RNA binding / 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 / serine-type endopeptidase activity / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / structural molecule activity / virion membrane / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) / Dengue virus type 2 / Dengue virus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 10.2 Å | |||||||||
Authors | 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 | United States, 2 items
| |||||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_29020.map.gz | 223.2 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-29020-v30.xml emd-29020.xml | 21.8 KB 21.8 KB | Display Display | EMDB header |
Images | emd_29020.png | 167.5 KB | ||
Filedesc metadata | emd-29020.cif.gz | 7 KB | ||
Others | emd_29020_half_map_1.map.gz emd_29020_half_map_2.map.gz | 223.1 MB 223.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29020 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29020 | HTTPS FTP |
-Validation report
Summary document | emd_29020_validation.pdf.gz | 890.1 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_29020_full_validation.pdf.gz | 889.6 KB | Display | |
Data in XML | emd_29020_validation.xml.gz | 22 KB | Display | |
Data in CIF | emd_29020_validation.cif.gz | 26.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29020 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29020 | HTTPS FTP |
-Related structure data
Related structure data | 8fe3MC 8fe4C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_29020.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.73 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #1
File | emd_29020_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_29020_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Mus musculus
Entire | Name: Mus musculus (house mouse) |
---|---|
Components |
|
-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 |
---|---|
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 |
---|---|
Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 24.6165 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 |
---|---|
Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.530898 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 |
---|---|
Source (natural) | Organism: Dengue virus type 2 |
Molecular weight | Theoretical: 43.892469 KDa |
Recombinant expression | Organism: Aedes albopictus (Asian tiger mosquito) |
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 |
---|---|
Source (natural) | Organism: Dengue virus type 2 |
Molecular weight | Theoretical: 9.261531 KDa |
Recombinant expression | Organism: Aedes albopictus (Asian tiger mosquito) |
Sequence | String: FHLTTRNGEP HMIVSRQEKG KSLLFKTEDG VNMCTLMAMD LGELCEDTIT YKCPLLRQNE PEDIDCWCNS TSTWVTYGTC T UniProtKB: Genome polyprotein |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL |
---|---|
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 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: FIELD EMISSION GUN |
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 |
-Image processing
Startup model | Type of model: INSILICO MODEL |
---|---|
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 |
| ||||||
---|---|---|---|---|---|---|---|
Refinement | Space: REAL / Protocol: RIGID BODY FIT | ||||||
Output model | PDB-8fe3: |