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Yorodumi- PDB-5uhy: A Human Antibody Against Zika Virus Crosslinks the E Protein to P... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5uhy | |||||||||||||||
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Title | A Human Antibody Against Zika Virus Crosslinks the E Protein to Prevent Infection | |||||||||||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / flavivirus / Zika / human antibody / therapeutic / VIRUS-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | Function and homology information 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 / negative regulation of innate immune response / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase ...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 / negative regulation of innate immune response / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / 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 / membrane => GO:0016020 / molecular adaptor activity / 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 / serine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / centrosome / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / host cell nucleus / virion attachment to host cell / GTP binding / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Zika virus | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.2 Å | |||||||||||||||
Authors | Hasan, S.S. / Miller, A. / Sapparapu, G. / Fernandez, E. / Klose, T. / Long, F. / Fokine, A. / Porta, J.C. / Jiang, W. / Diamond, M.S. ...Hasan, S.S. / Miller, A. / Sapparapu, G. / Fernandez, E. / Klose, T. / Long, F. / Fokine, A. / Porta, J.C. / Jiang, W. / Diamond, M.S. / Crowe Jr., J.E. / Kuhn, R.J. / Rossmann, M.G. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nat Commun / Year: 2017 Title: A human antibody against Zika virus crosslinks the E protein to prevent infection. Authors: S Saif Hasan / Andrew Miller / Gopal Sapparapu / Estefania Fernandez / Thomas Klose / Feng Long / Andrei Fokine / Jason C Porta / Wen Jiang / Michael S Diamond / James E Crowe / Richard J ...Authors: S Saif Hasan / Andrew Miller / Gopal Sapparapu / Estefania Fernandez / Thomas Klose / Feng Long / Andrei Fokine / Jason C Porta / Wen Jiang / Michael S Diamond / James E Crowe / Richard J Kuhn / Michael G Rossmann / Abstract: The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. ...The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes. | |||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 5uhy.cif.gz | 376.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5uhy.ent.gz | 298.8 KB | Display | PDB format |
PDBx/mmJSON format | 5uhy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5uhy_validation.pdf.gz | 989.8 KB | Display | wwPDB validaton report |
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Full document | 5uhy_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5uhy_validation.xml.gz | 85.9 KB | Display | |
Data in CIF | 5uhy_validation.cif.gz | 124.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uh/5uhy ftp://data.pdbj.org/pub/pdb/validation_reports/uh/5uhy | HTTPS FTP |
-Related structure data
Related structure data | 8548MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Antibody | Mass: 23658.074 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #2: Antibody | Mass: 23074.842 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Protein | Mass: 43123.906 Da / Num. of mol.: 3 / Fragment: ectodomain (UNP residues 1-396) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zika virus / Production host: Cricetinae gen. sp. (mammal) / References: UniProt: A0A120IIH7, UniProt: A0A024B7W1*PLUS |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Zika virus with ZIKV117 Fab / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Zika virus | ||||||||||||||||||||
Details of virus | Empty: NO / Enveloped: YES / Isolate: SPECIES / Type: VIRION | ||||||||||||||||||||
Natural host | Organism: Homo sapiens | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: 1 mg/mL E protein | ||||||||||||||||||||
Specimen support | Details: no pretreatment / Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Ted Pella 01824 | ||||||||||||||||||||
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 80 % / Chamber temperature: 293 K Details: 2.5 uL of sample was deposited on the carbon layer, with double-sided blotting applied twice for 5-6 seconds. |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 18000 X / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 11 sec. / Electron dose: 32.6 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1140 |
Image scans | Width: 3838 / Height: 3710 / Movie frames/image: 55 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8153 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT |