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Yorodumi- EMDB-7345: An anti-gH/gL antibody that neutralizes dual-tropic infection def... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7345 | |||||||||
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Title | An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus | |||||||||
Map data | An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus | |||||||||
Sample |
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Biological species | Human herpesvirus 4 (Epstein-Barr virus) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 10.0 Å | |||||||||
Authors | Snijder J / Ortego MS | |||||||||
Citation | Journal: Immunity / Year: 2018 Title: An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus. Authors: Joost Snijder / Michael S Ortego / Connor Weidle / Andrew B Stuart / Matthew D Gray / M Juliana McElrath / Marie Pancera / David Veesler / Andrew T McGuire / Abstract: Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have ...Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden. | |||||||||
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_7345.map.gz | 526.6 KB | EMDB map data format | |
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Header (meta data) | emd-7345-v30.xml emd-7345.xml | 13.6 KB 13.6 KB | Display Display | EMDB header |
Images | emd_7345.png | 34.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7345 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7345 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_7345.map.gz / Format: CCP4 / Size: 5.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.72 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Epstein-Barr virus glycoproteins H,L,42 in complex with the human...
Entire | Name: Epstein-Barr virus glycoproteins H,L,42 in complex with the human antibody Fab fragment AMMO1. |
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Components |
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-Supramolecule #1: Epstein-Barr virus glycoproteins H,L,42 in complex with the human...
Supramolecule | Name: Epstein-Barr virus glycoproteins H,L,42 in complex with the human antibody Fab fragment AMMO1. type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Epstein-Barr viral protein
Supramolecule | Name: Epstein-Barr viral protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Human herpesvirus 4 (Epstein-Barr virus) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: 293 |
-Supramolecule #3: Human antibody
Supramolecule | Name: Human antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: 293 |
-Macromolecule #1: Epstein-barr virus glycoprotein H
Macromolecule | Name: Epstein-barr virus glycoprotein H / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSASSLSEV KLHLDIEGHA SHYTIPWTEL MAKVPGLSPE ALWREANVTE DLASMLNRYK LIYKTSGTLG IALAEPVDIP AVSEGSMQVD ASKVHPGVIS GLNSPACMLS APLEKQLFYY IGTMLPNTRP HSYVFYQLRC HLSYVALSIN ...String: MDAMKRGLCC VLLLCGAVFV SPSASSLSEV KLHLDIEGHA SHYTIPWTEL MAKVPGLSPE ALWREANVTE DLASMLNRYK LIYKTSGTLG IALAEPVDIP AVSEGSMQVD ASKVHPGVIS GLNSPACMLS APLEKQLFYY IGTMLPNTRP HSYVFYQLRC HLSYVALSIN GDKFQYTGAM TSKFLMGTYK RVTEKGDEHV LSLVFGKTKD LPDLRGPFSY PSLTSAQSGD YSLVIVTTFV HYANFHNYFV PNLKDMFSRA VTMTAASYAR YVLQKLVLLE MKGGCREPEL DTETLTTMFE VSVAFFKVGH AVGETGNGCV DLRWLAKSFF ELTVLKDIIG ICYGATVKGM QSYGLERLAA MLMATVKMEE LGHLTTEKQE YALRLATVGY PKAGVYSGLI GGATSVLLSA YNRHPLFQPL HTVMRETLFI GSHVVLRELR LNVTTQGPNL ALYQLLSTAL CSALEIGEVL RGLALGTESG LFSPCYLSLR FDLTRDKLLS MAPQEATLDQ AAVSYAVDGF LGRLSLERED RDAWHLPAYK CVDRLDKVLM IIPLINVTFI ISSDREVRGS ALYEASTTYL SSSLFLSPVI MNKCSQGAVA GEPRQIPKIQ NFTRTQKSCI FCGFALLSYD EKEGLETTTY ITSQEVQNSI LSSNYFDFDN LHVHYLLLTT NGTVMEIAGL YEERAHGSGS GHHHHHH |
-Macromolecule #2: Epstein-barr virus glycoprotein L
Macromolecule | Name: Epstein-barr virus glycoprotein L / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSASWAYPC CHVTQLRAQH LLALENISDI YLVSNQTCDG FSLASLNSPK NGSNQLVISR CANGLNVVSF FISILKRSSS ALTGHLRELL TTLETLYGSF SVEDLFGANL NRYAWHRGG |
-Macromolecule #3: Epstein-barr virus glycoprotein 42
Macromolecule | Name: Epstein-barr virus glycoprotein 42 / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSASGGGRV AAAAITWVPK PNVEVWPVDP PPPVNFNKTA EQEYGDKEVK LPHWTPTLHT FQVPQNYTKA NCTYCNTREY TFSYKGCCFY FTKKKHTWNG CFQACAELYP CTYFYGPTPD ILPVVTRNLN AIESLWVGVY RVGEGNWTSL ...String: MDAMKRGLCC VLLLCGAVFV SPSASGGGRV AAAAITWVPK PNVEVWPVDP PPPVNFNKTA EQEYGDKEVK LPHWTPTLHT FQVPQNYTKA NCTYCNTREY TFSYKGCCFY FTKKKHTWNG CFQACAELYP CTYFYGPTPD ILPVVTRNLN AIESLWVGVY RVGEGNWTSL DGGTFKVYQI FGSHCTYVSK FSTVPVSHHE CSFLKPCLCV SQRSNSGSGS GHHHHHH |
-Macromolecule #4: Human antibody AMMO1 heavy chain
Macromolecule | Name: Human antibody AMMO1 heavy chain / type: protein_or_peptide / ID: 4 / Enantiomer: LEVO |
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Sequence | String: (PCA)VQLVQSGAD VKKPGASVK V SCKASGYT FI HFGISWV RQA PGQGLE WMGW IDTNN GNTNY AQSL QGRVTM TTD TSTGTAY ME LRSLSTDD T AVYFCARAL EMGHRSGFPF DYWGQGVLV T VSPASTKG PS VFPLAPS SKS TSGGTA ALGC LVKDY ...String: (PCA)VQLVQSGAD VKKPGASVK V SCKASGYT FI HFGISWV RQA PGQGLE WMGW IDTNN GNTNY AQSL QGRVTM TTD TSTGTAY ME LRSLSTDD T AVYFCARAL EMGHRSGFPF DYWGQGVLV T VSPASTKG PS VFPLAPS SKS TSGGTA ALGC LVKDY FPEPV TVSW NSGALT SGV HTFPAVL QS SGLYSLSS V VTVPSSSLG TQTYICNVNH KPSNTKVDK R VEPKSC |
-Macromolecule #5: Human antibody AMMO1 light chain
Macromolecule | Name: Human antibody AMMO1 light chain / type: protein_or_peptide / ID: 5 / Enantiomer: LEVO |
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Sequence | String: SYELTQPPSV SVAPGQRATI TCGGHNIGAK NVHWYQQKPG QAPVLVIQYD SDRPSGIPER FSGSNSGSTA TLTISRVEAG DEADYYCQVW DSGRGHPLYV FGGGTKVTVL GQPKANPTVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK ...String: SYELTQPPSV SVAPGQRATI TCGGHNIGAK NVHWYQQKPG QAPVLVIQYD SDRPSGIPER FSGSNSGSTA TLTISRVEAG DEADYYCQVW DSGRGHPLYV FGGGTKVTVL GQPKANPTVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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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) / Detector mode: COUNTING / Average electron dose: 65.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: PROJECTION MATCHING |
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Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 10.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 72000 |