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Yorodumi- PDB-6tys: A potent cross-neutralizing antibody targeting the fusion glycopr... -
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-Basic information
Entry | Database: PDB / ID: 6tys | |||||||||
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Title | A potent cross-neutralizing antibody targeting the fusion glycoprotein inhibits Nipah virus and Hendra virus infection | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Henipavirus / Nipah virus / Hendra virus / fusion glycoprotein / antibody / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information membrane fusion involved in viral entry into host cell / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | Nipah virus Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Dang, H.V. / Chan, Y.P. / Park, Y.J. / Snijder, J. / Da Silva, S.C. / Vu, B. / Yan, L. / Feng, Y.R. / Rockx, B. / Geisbert, T. ...Dang, H.V. / Chan, Y.P. / Park, Y.J. / Snijder, J. / Da Silva, S.C. / Vu, B. / Yan, L. / Feng, Y.R. / Rockx, B. / Geisbert, T. / Mire, C.E. / Broder, C.B. / Veesler, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2019 Title: An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Authors: Ha V Dang / Yee-Peng Chan / Young-Jun Park / Joost Snijder / Sofia Cheliout Da Silva / Bang Vu / Lianying Yan / Yan-Ru Feng / Barry Rockx / Thomas W Geisbert / Chad E Mire / Christopher C ...Authors: Ha V Dang / Yee-Peng Chan / Young-Jun Park / Joost Snijder / Sofia Cheliout Da Silva / Bang Vu / Lianying Yan / Yan-Ru Feng / Barry Rockx / Thomas W Geisbert / Chad E Mire / Christopher C Broder / David Veesler / Abstract: Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed ...Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals. | |||||||||
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 | 6tys.cif.gz | 393.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6tys.ent.gz | 326.2 KB | Display | PDB format |
PDBx/mmJSON format | 6tys.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ty/6tys ftp://data.pdbj.org/pub/pdb/validation_reports/ty/6tys | HTTPS FTP |
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-Related structure data
Related structure data | 20584MC 6u1tC 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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1 |
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-Components
-Protein , 1 types, 3 molecules ABE
#1: Protein | Mass: 59704.781 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Nipah virus / Production host: Homo sapiens (human) / References: UniProt: Q9IH63 |
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-Antibody , 2 types, 6 molecules HCFLDG
#2: Antibody | Mass: 13245.752 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) #3: Antibody | Mass: 11517.844 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Igkv12-98 / Production host: Mus musculus (house mouse) |
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-Sugars , 4 types, 18 molecules
#4: Polysaccharide | alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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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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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
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: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 38721 / Symmetry type: POINT |