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Yorodumi- EMDB-20584: A potent cross-neutralizing antibody targeting the fusion glycopr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20584 | |||||||||
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Title | A potent cross-neutralizing antibody targeting the fusion glycoprotein inhibits Nipah virus and Hendra virus infection | |||||||||
Map data | Sharpened map | |||||||||
Sample |
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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 | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Dang HV / Chan YP / Park YJ / Snijder J / Da Silva SC / Vu B / Yan L / Feng YR / Rockx B / Geisbert T ...Dang HV / Chan YP / Park YJ / Snijder J / Da Silva SC / Vu B / Yan L / Feng YR / Rockx B / Geisbert T / Mire CE / Broder CB / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | United States, 1 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20584.map.gz | 2.1 MB | EMDB map data format | |
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Header (meta data) | emd-20584-v30.xml emd-20584.xml | 16.7 KB 16.7 KB | Display Display | EMDB header |
Images | emd_20584.png | 171.4 KB | ||
Others | emd_20584_additional.map.gz | 32.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20584 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20584 | HTTPS FTP |
-Validation report
Summary document | emd_20584_validation.pdf.gz | 325.6 KB | Display | EMDB validaton report |
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Full document | emd_20584_full_validation.pdf.gz | 325.2 KB | Display | |
Data in XML | emd_20584_validation.xml.gz | 6.3 KB | Display | |
Data in CIF | emd_20584_validation.cif.gz | 7.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20584 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20584 | HTTPS FTP |
-Related structure data
Related structure data | 6tysMC 6u1tC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20584.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.37 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_20584_additional.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Nipah virus fusion (F) glycoprotein in complex with the 5B3 antib...
Entire | Name: Nipah virus fusion (F) glycoprotein in complex with the 5B3 antibody Fab fragment |
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Components |
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-Supramolecule #1: Nipah virus fusion (F) glycoprotein in complex with the 5B3 antib...
Supramolecule | Name: Nipah virus fusion (F) glycoprotein in complex with the 5B3 antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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-Supramolecule #2: Fusion glycoprotein F0
Supramolecule | Name: Fusion glycoprotein F0 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Nipah virus |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: 5B3 antibody
Supramolecule | Name: 5B3 antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Fusion glycoprotein F0
Macromolecule | Name: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Nipah virus |
Molecular weight | Theoretical: 59.704781 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTP IKGALEIYKN CTHDLDYKDD DDKVGDVRLA GVIMAGVCIG IATAAQITAG VALYEAMKNA DNINKLKSSI E STNEAVVK ...String: MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTP IKGALEIYKN CTHDLDYKDD DDKVGDVRLA GVIMAGVCIG IATAAQITAG VALYEAMKNA DNINKLKSSI E STNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA IS QAFGGNY ETLLRTLGYA TEDFDDLLES DSITGQIIYV DLSSYYIIVR VYFPILTEIQ QAYIQELLPV SFNNDNSEWI SIV PNFILV RNTLISNIEI GFCLITKRSV ICNQDYATPM TNNMRECLTG STEKCPRELV VSSHVPRFAL SNGVLFANCI SVTC QCQTT GRAISQSGEQ TLLMIDNTTC PTAVLGNVII SLGKYLGSVN YNSEGIAIGP PVFTDKVDIS SQISSMNQSL QQSKD YIKE AQRLLDTVNP SLISMLSMMK QIEDKIEEIL SKIYHIENEI ARIKKLIGER IDGR |
-Macromolecule #2: 5B3 antibody heavy chain
Macromolecule | Name: 5B3 antibody heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 13.245752 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: EVQLVESGGG LVKPGGSLKL SCAASGFTFS SYDMSWVRQT PEKRLEWVAM ISSGGSYSYY PDSVKGRFTI SRDNAKNTLY LQMSSLRSE DTAMYYCARQ GDYAWFAYWG QGTLVTVSSA S |
-Macromolecule #3: 5B3 antibody light chain
Macromolecule | Name: 5B3 antibody light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 11.517844 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: DIQMTQSPAS QSASLGESVT ITCLASQTIG TWLAWYQQKP GKSPQLLIYA ATSLADGVPS RFSGSGSGTK FSFKISSLQA EDFVSYYCQ QFYSTPFTFG GGTKLEIK |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 6 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 38721 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |