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- PDB-8fe4: Structure of dengue virus (DENV2) in complex with prM13, an anti-... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8fe4 | |||||||||
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Title | Structure of dengue virus (DENV2) in complex with prM13, an anti-PrM monoclonal antibody | |||||||||
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![]() | VIRUS/IMMUNE SYSTEM / DENV / ![]() | |||||||||
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 / ribonucleoside triphosphate phosphatase activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Dowd, A.D. / Sirohi, D. / Speer, S. / Mukherjee, S. / Govero, J. / Aleshnick, M. / Larman, B. / Sukupolvi-Petty, S. / Sevvana, M. / Miller, A.S. ...Dowd, A.D. / Sirohi, D. / Speer, S. / Mukherjee, S. / Govero, J. / Aleshnick, M. / Larman, B. / Sukupolvi-Petty, S. / Sevvana, M. / Miller, A.S. / Klose, T. / Zheng, A. / Kielian, M. / Kuhn, R.J. / Diamond, M.S. / Pierson, T.C. | |||||||||
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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 396.4 KB | Display | ![]() |
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PDB format | ![]() | 280.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 29021MC ![]() 8fe3C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Symmetry | Point symmetry: (Schoenflies symbol![]() ![]() |
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Components
#1: Protein | ![]() Mass: 43892.469 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #2: Protein | Mass: 9261.531 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #3: Antibody | Mass: 23777.656 Da / Num. of mol.: 3 / Mutation: X1A,X2A Source method: isolated from a genetically manipulated source Details: The homology model of the prM13 variable heavy chain domain (1-118) 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 prM13 variable heavy chain domain (1-118) 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 prM13. Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #4: Antibody | Mass: 23245.510 Da / Num. of mol.: 3 / Mutation: X1A,X4A,X106A,X103A Source method: isolated from a genetically manipulated source Details: The homology model of the prM13 variable light chain domain (1-106) 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 prM13 variable light chain domain (1-106) 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 prM13. Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Mus musculus![]() | ||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||
Source (natural) |
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Source (recombinant) |
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Details of virus | Empty: NO / Enveloped: YES / Isolate: SEROTYPE / Type: VIRION | ||||||||||||
Virus shell | Diameter: 500 nm / Triangulation number (T number): 3 | ||||||||||||
Buffer solution | pH: 8 | ||||||||||||
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: PELCO Ultrathin Carbon with Lacey Carbon | ||||||||||||
Vitrification![]() | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 30 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Symmetry | Point symmetry![]() ![]() | ||||||||||||
3D reconstruction![]() | Resolution: 9.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 5458 / Symmetry type: POINT | ||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||
Atomic model building |
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Refinement | Highest resolution: 9.8 Å |