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Yorodumi- PDB-7kcr: Cryo-EM structure of Zika virus in complex with E protein cross-l... -
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-Basic information
Entry | Database: PDB / ID: 7kcr | |||||||||
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Title | Cryo-EM structure of Zika virus in complex with E protein cross-linking human monoclonal antibody ADI30056 | |||||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / Zika Virus / Flavivirus / Zika-Antibody / VIRUS-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information response to herbicide / photosystem II / flavivirin / chlorophyll binding / plasma membrane-derived thylakoid membrane / electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity / photosynthetic electron transport in photosystem II / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / membrane => GO:0016020 ...response to herbicide / photosystem II / flavivirin / chlorophyll binding / plasma membrane-derived thylakoid membrane / electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity / photosynthetic electron transport in photosystem II / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / membrane => GO:0016020 / double-stranded RNA binding / nucleoside-triphosphate phosphatase / viral capsid / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / protein dimerization activity / host cell endoplasmic reticulum membrane / RNA helicase / 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 / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / extracellular region / ATP binding / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
Authors | Sevvana, M. / Rogers, T.F. / Miller, A.S. / Long, F. / Klose, T. / Beutler, N. / Lai, Y.C. / Parren, M. / Walker, L.M. / Buda, G. ...Sevvana, M. / Rogers, T.F. / Miller, A.S. / Long, F. / Klose, T. / Beutler, N. / Lai, Y.C. / Parren, M. / Walker, L.M. / Buda, G. / Burton, D.R. / Rossmann, M.G. / Kuhn, R.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Viruses / Year: 2020 Title: Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections. Authors: Madhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G ...Authors: Madhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G Rossmann / Richard J Kuhn / Abstract: Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We ...Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies. | |||||||||
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 | 7kcr.cif.gz | 330.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7kcr.ent.gz | 278.9 KB | Display | PDB format |
PDBx/mmJSON format | 7kcr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7kcr_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7kcr_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7kcr_validation.xml.gz | 81.1 KB | Display | |
Data in CIF | 7kcr_validation.cif.gz | 116 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kc/7kcr ftp://data.pdbj.org/pub/pdb/validation_reports/kc/7kcr | HTTPS FTP |
-Related structure data
Related structure data | 22818MC 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: 13467.001 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Scheffersomyces stipitis (fungus) | ||||||
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#2: Antibody | Mass: 11385.728 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Scheffersomyces stipitis (fungus) | ||||||
#3: Protein | Mass: 54186.762 Da / Num. of mol.: 3 / Fragment: UNP residues 291-791 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 Production host: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 References: UniProt: A0A678Z1Y6, UniProt: A0A024B7W1*PLUS #4: Protein | Mass: 8496.883 Da / Num. of mol.: 3 / Fragment: UNP residues 216-290 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 Production host: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 References: UniProt: A0A678Z1Y6, UniProt: A0A024B7W1*PLUS #5: Polysaccharide | Source method: isolated from a genetically manipulated source Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: 2D ARRAY / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Value: 15 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Details of virus | Empty: NO / Enveloped: YES / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||
Natural host | Organism: Homo sapiens | ||||||||||||||||||||||||
Virus shell | Name: Envelope protein shell / Diameter: 500 nm / Triangulation number (T number): 3 | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
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: OTHER |
Electron lens | Mode: BRIGHT FIELD / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 165789 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 22330 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6CO8 | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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