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Yorodumi- EMDB-22885: Structure of the HeV F glycoprotein in complex with the 1F5 neutr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22885 | |||||||||
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Title | Structure of the HeV F glycoprotein in complex with the 1F5 neutralizing antibody | |||||||||
Map data | Sharpened map | |||||||||
Sample |
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Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / membrane => GO:0016020 / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0 Function and homology information | |||||||||
Biological species | Hendra henipavirus / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Dang HV / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler D | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins. Authors: Ha V Dang / Robert W Cross / Viktoriya Borisevich / Zachary A Bornholdt / Brandyn R West / Yee-Peng Chan / Chad E Mire / Sofia Cheliout Da Silva / Antony S Dimitrov / Lianying Yan / Moushimi ...Authors: Ha V Dang / Robert W Cross / Viktoriya Borisevich / Zachary A Bornholdt / Brandyn R West / Yee-Peng Chan / Chad E Mire / Sofia Cheliout Da Silva / Antony S Dimitrov / Lianying Yan / Moushimi Amaya / Chanakha K Navaratnarajah / Larry Zeitlin / Thomas W Geisbert / Christopher C Broder / David Veesler / Abstract: Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50-100%. There are no licensed therapeutics or ...Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50-100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses. | |||||||||
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_22885.map.gz | 3.8 MB | EMDB map data format | |
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Header (meta data) | emd-22885-v30.xml emd-22885.xml | 20.5 KB 20.5 KB | Display Display | EMDB header |
Images | emd_22885.png | 133.2 KB | ||
Others | emd_22885_additional_1.map.gz emd_22885_half_map_1.map.gz emd_22885_half_map_2.map.gz | 83.4 MB 154.4 MB 154.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22885 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22885 | HTTPS FTP |
-Validation report
Summary document | emd_22885_validation.pdf.gz | 823.3 KB | Display | EMDB validaton report |
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Full document | emd_22885_full_validation.pdf.gz | 822.8 KB | Display | |
Data in XML | emd_22885_validation.xml.gz | 15 KB | Display | |
Data in CIF | emd_22885_validation.cif.gz | 17.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22885 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22885 | HTTPS FTP |
-Related structure data
Related structure data | 7ki6MC 7ki4C 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_22885.map.gz / Format: CCP4 / Size: 166.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 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_22885_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_22885_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_22885_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HeV F glycoprotein in complex with the 1F5 neutralizing antibody ...
Entire | Name: HeV F glycoprotein in complex with the 1F5 neutralizing antibody Fab fragment |
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Components |
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-Supramolecule #1: HeV F glycoprotein in complex with the 1F5 neutralizing antibody ...
Supramolecule | Name: HeV F glycoprotein in complex with the 1F5 neutralizing antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Hendra henipavirus |
Recombinant expression | Organism: Homo sapiens (human) |
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: Hendra henipavirus |
Molecular weight | Theoretical: 59.631574 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MATQEVRLKC LLCGIIVLVL SLEGLGILHY EKLSKIGLVK GITRKYKIKS NPLTKDIVIK MIPNVSNVSK CTGTVMENYK SRLTGILSP IKGAIELYNN NTHDLVGDVK LAGVVMAGIA IGIATAAQIT AGVALYEAMK NADNINKLKS SIESTNEAVV K LQETAEKT ...String: MATQEVRLKC LLCGIIVLVL SLEGLGILHY EKLSKIGLVK GITRKYKIKS NPLTKDIVIK MIPNVSNVSK CTGTVMENYK SRLTGILSP IKGAIELYNN NTHDLVGDVK LAGVVMAGIA IGIATAAQIT AGVALYEAMK NADNINKLKS SIESTNEAVV K LQETAEKT VYVLTALQDY INTNLVPTID QISCKQTELA LDLALSKYLS DLLFVFGPNL QDPVSNSMTI QAISQAFGGN YE TLLRTLG YATEDFDDLL ESDSIAGQIV YVDLSSYYII VRVYFPILTE IQQAYVQELL PVSFNNDNSE WISIVPNFVL IRN TLISNI EVKYCLITKK SVICNQDYAT PMTASVRECL TGSTDKCPRE LVVSSHVPRF ALSGGVLFAN CISVTCQCQT TGRA ISQSG EQTLLMIDNT TCTTVVLGNI IISLGKYLGS INYNSESIAV GPPVYTDKVD ISSQISSMNQ SLQQSKDYIK EAQKI LDTV NPSMKQIEDK IEEILSKIYH IENEIARIKK LIGEAPGGIE GRKLKETAAA KFERQHMDS |
-Macromolecule #2: 1F5 Fab light chain
Macromolecule | Name: 1F5 Fab light 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: 23.362713 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: QIVLTQSPAI MSASLGEAIT LTCSASSSVS YMHWYQQKSG TSPKLLIYST SNLASGVPSR FSGSGSGTFY SLTISSVEAE DAADYYCHQ WYSYPWTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK ...String: QIVLTQSPAI MSASLGEAIT LTCSASSSVS YMHWYQQKSG TSPKLLIYST SNLASGVPSR FSGSGSGTFY SLTISSVEAE DAADYYCHQ WYSYPWTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK DSTYSMSSTL TLTKDEYERH NSYTCEATHK TSTSPIVKSF NRNEC |
-Macromolecule #3: 1F5 heavy chain
Macromolecule | Name: 1F5 heavy 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: 49.291246 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: DVQLQESGPG LVKPSQSLSL TCSVTGYSIT SDYYWNWIRQ FPGNKLEWMG YVTYDGSNNY NPSLKNRISI TRDSSKNQFF LKLNSVISE DTATYYCARF GSSYWAMDYW GQGTSLTVSS AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG ...String: DVQLQESGPG LVKPSQSLSL TCSVTGYSIT SDYYWNWIRQ FPGNKLEWMG YVTYDGSNNY NPSLKNRISI TRDSSKNQFF LKLNSVISE DTATYYCARF GSSYWAMDYW GQGTSLTVSS AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG VHTFPAVLQS DLYTLSSSVT VPSSTWPSET VTCNVAHPAS STKVDKKIVP RDCGCKPCIC TVPEVSSVFI FP PKPKDVL TITLTPKVTC VVVDISKDDP EVQFSWFVDD VEVHTAQTQP REEQFNSTFR SVSELPIMHQ DWLNGKEFKC RVN SAAFPA PIEKTISKTK GRPKAPQVYT IPPPKEQMAK DKVSLTCMIT DFFPEDITVE WQWNGQPAEN YKNTQPIMDT DGSY FVYSK LNVQKSNWEA GNTFTCSVLH EGLHNHHTEK SLSHSPGK |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / 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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Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Support film - Material: CARBON |
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: 70.0 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
Startup model | Type of model: OTHER / Details: cryoSPARC ab initio |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 34415 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |