+Open data
-Basic information
Entry | Database: PDB / ID: 5h32 | ||||||||||||
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Title | Cryo-EM structure of zika virus complexed with Fab C10 at pH 5.0 | ||||||||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / Antibody / 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 / 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: 12 Å | ||||||||||||
Authors | Zhang, S. / Kostyuchenko, V. / Ng, T.-S. / Lok, S.-M. | ||||||||||||
Funding support | Singapore, United States, 3items
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Citation | Journal: Nat Commun / Year: 2016 Title: Neutralization mechanism of a highly potent antibody against Zika virus. Authors: Shuijun Zhang / Victor A Kostyuchenko / Thiam-Seng Ng / Xin-Ni Lim / Justin S G Ooi / Sebastian Lambert / Ter Yong Tan / Douglas G Widman / Jian Shi / Ralph S Baric / Shee-Mei Lok / Abstract: The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies ...The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event-a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate. | ||||||||||||
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 | 5h32.cif.gz | 72.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5h32.ent.gz | 45.5 KB | Display | PDB format |
PDBx/mmJSON format | 5h32.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5h32_validation.pdf.gz | 828.7 KB | Display | wwPDB validaton report |
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Full document | 5h32_full_validation.pdf.gz | 828.3 KB | Display | |
Data in XML | 5h32_validation.xml.gz | 27.7 KB | Display | |
Data in CIF | 5h32_validation.cif.gz | 41.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h3/5h32 ftp://data.pdbj.org/pub/pdb/validation_reports/h3/5h32 | HTTPS FTP |
-Related structure data
Related structure data | 9574MC 9573C 9575C 5h30C 5h37C 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: Protein | Mass: 44069.930 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Zika virus / Strain: Mr 766 / References: UniProt: A0A024B7W1 #2: Antibody | Mass: 14487.058 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293T / Production host: Homo sapiens (human) #3: Antibody | Mass: 11298.362 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293T / Production host: Homo sapiens (human) |
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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 |
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Source (natural) | Organism: Zika virus | ||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293T / Plasmid: unknown | ||||||||||||||||||||||||
Buffer solution | pH: 5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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 |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 12 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 23810 / Symmetry type: POINT |