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Yorodumi- EMDB-22884: Structure of the NiV F glycoprotein in complex with the 12B2 neut... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22884 | |||||||||
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Title | Structure of the NiV F glycoprotein in complex with the 12B2 neutralizing antibody | |||||||||
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: 2.9 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_22884.map.gz | 4.4 MB | EMDB map data format | |
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Header (meta data) | emd-22884-v30.xml emd-22884.xml | 20.3 KB 20.3 KB | Display Display | EMDB header |
Images | emd_22884.png | 71.6 KB | ||
Others | emd_22884_additional_1.map.gz emd_22884_half_map_1.map.gz emd_22884_half_map_2.map.gz | 83.9 MB 154.2 MB 154.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22884 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22884 | HTTPS FTP |
-Related structure data
Related structure data | 7ki4MC 7ki6C 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_22884.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_22884_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_22884_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_22884_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : NiV F glycoprotein in complex with the 12B2 neutralizing antibody...
Entire | Name: NiV F glycoprotein in complex with the 12B2 neutralizing antibody Fab fragment |
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Components |
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-Supramolecule #1: NiV F glycoprotein in complex with the 12B2 neutralizing antibody...
Supramolecule | Name: NiV F glycoprotein in complex with the 12B2 neutralizing antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Nipah virus |
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: Nipah virus |
Molecular weight | Theoretical: 60.028074 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTP IKGALEIYKN NTHDLVGDVR LAGVIMAGVA IGIATAAQIT AGVALYEAMK NADNINKLKS SIESTNEAVV K LQETAEKT ...String: MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTP IKGALEIYKN NTHDLVGDVR LAGVIMAGVA IGIATAAQIT AGVALYEAMK NADNINKLKS SIESTNEAVV K LQETAEKT VYVLTALQDY INTNLVPTID KISCKQTELS LDLALSKYLS DLLFVFGPNL QDPVSNSMTI QAISQAFGGN YE TLLRTLG YATEDFDDLL ESDSITGQII YVDLSSYYII VRVYFPILTE IQQAYIQELL PVSFNNDDSE WISIVPNFIL VRN TLISNI EIGFCLITKR SVICNQDYAT PMTNNMRECL TGSTEKCPRE LVVSSHVPRF ALSNGVLFAN CISVTCQCQT TGRA ISQSG EQTLLMIDNT TCPTAVLGNV IISLGKYLGS VNYNSEGIAI GPPVFTDKVD ISSQISSMNQ SLQQSKDYIK EAQRL LDTV NPSMKQIEDK IEEILSKIYH IENEIARIKK LIGEAPGGIE GRKLKETAAA KFERQHMDS |
-Macromolecule #2: 12B2 Fab light chain
Macromolecule | Name: 12B2 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: 23.657051 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: DIQMTQSPAS LSASVGETVT ITCRASENIY SYLAWYQHKQ GKSPQLLVYN AKSLAEGVPS RFSGSGSGTQ FSLKINSLQP EDFGSYYCQ HHYGTPWTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String: DIQMTQSPAS LSASVGETVT ITCRASENIY SYLAWYQHKQ GKSPQLLVYN AKSLAEGVPS RFSGSGSGTQ FSLKINSLQP EDFGSYYCQ HHYGTPWTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNEC |
-Macromolecule #3: 12B2 heavy chain
Macromolecule | Name: 12B2 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: 48.630758 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: QVQLKESGPG LVAPSQSLSI TCTVSGFSLA SYGVHWVRQP PGKGLEWLGV IWTGGSTNYN SALMSRLSIN RDNSKSQVFL KLNSLQTDD TAIYYCARDR GYGYGGFAYW GQGTLVTVSA AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG ...String: QVQLKESGPG LVAPSQSLSI TCTVSGFSLA SYGVHWVRQP PGKGLEWLGV IWTGGSTNYN SALMSRLSIN RDNSKSQVFL KLNSLQTDD TAIYYCARDR GYGYGGFAYW GQGTLVTVSA 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 |
-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 / Mesh: 200 / Support film - Material: CARBON |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2 |
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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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 28776 |