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Yorodumi- PDB-6jep: Structure of a neutralizing antibody bound to the Zika envelope p... -
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-Basic information
Entry | Database: PDB / ID: 6jep | ||||||
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Title | Structure of a neutralizing antibody bound to the Zika envelope protein domain III | ||||||
Components |
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Keywords | ANTIVIRAL PROTEIN / Antibody / complex | ||||||
Function / homology | Function and homology information flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / membrane => GO:0016020 ...flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / membrane => GO:0016020 / host cell endoplasmic reticulum membrane / protein dimerization activity / RNA helicase / induction by virus of host autophagy / viral RNA genome replication / RNA-dependent RNA polymerase activity / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / virion attachment to host cell / virion membrane / structural molecule activity / extracellular region / ATP binding / metal ion binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Zika virus | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.316 Å | ||||||
Authors | Wang, L. / Wang, R.K. / Wang, L. / Ben, H.J. / Yu, L. / Gao, F. / Shi, X.L. / Yin, C.B. / Zhang, F.C. / Xiang, Y. / Zhang, L.Q. | ||||||
Citation | Journal: Cell Rep / Year: 2019 Title: Structural Basis for Neutralization and Protection by a Zika Virus-Specific Human Antibody. Authors: Lin Wang / Ruoke Wang / Lei Wang / Haijing Ben / Lei Yu / Fei Gao / Xuanling Shi / Chibiao Yin / Fuchun Zhang / Ye Xiang / Linqi Zhang / Abstract: We previously reported a human monoclonal antibody, ZK2B10, capable of protection against Zika virus (ZIKV) infection and microcephaly in developing mouse embryos. Here, we report the structural ...We previously reported a human monoclonal antibody, ZK2B10, capable of protection against Zika virus (ZIKV) infection and microcephaly in developing mouse embryos. Here, we report the structural features and mechanism of action of ZK2B10. The crystal structure at a resolution of 2.32 Å revealed that the epitope is located on the lateral ridge of DIII of the envelope glycoprotein. Cryo-EM structure with mature ZIKV showed that the antibody binds to DIIIs around the icosahedral 2-fold, 3-fold, and 5-fold axes, a distinct feature compared to those reported for DIII-specific antibodies. The binding of ZK2B10 to ZIKV has no detectable effect on viral attachment to target cells or on conformational changes of the E glycoprotein in the acidic environment, suggesting that ZK2B10 functions at steps between the formation of the fusion intermediate and membrane fusion. These results provide structural and mechanistic insights into how ZK2B10 mediates protection against ZIKV infection. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6jep.cif.gz | 417.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6jep.ent.gz | 352.8 KB | Display | PDB format |
PDBx/mmJSON format | 6jep.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/je/6jep ftp://data.pdbj.org/pub/pdb/validation_reports/je/6jep | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
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-Components
#1: Antibody | Mass: 25383.305 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: 22782.035 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: 10989.564 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zika virus / Production host: Escherichia coli K-12 (bacteria) / Strain (production host): K-12 / References: UniProt: A0A2Z2ESG6 #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.5 Å3/Da / Density % sol: 50.71 % |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, hanging drop / Details: MPD, PEG1500, Sodium acetate/Acetic acid |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.97915 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: May 28, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97915 Å / Relative weight: 1 |
Reflection | Resolution: 2.316→35.646 Å / Num. obs: 50308 / % possible obs: 99.72 % / Redundancy: 3.7 % / Net I/σ(I): 16.15 |
Reflection shell | Resolution: 2.32→2.36 Å |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.316→35.646 Å / SU ML: 0.29 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 23.94 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 114.88 Å2 / Biso mean: 36.8256 Å2 / Biso min: 14.29 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.316→35.646 Å
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Refine LS restraints NCS |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 17
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Refinement TLS params. | Method: refined / Origin x: -13.4998 Å / Origin y: 20.4834 Å / Origin z: -17.4096 Å
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Refinement TLS group |
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