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- EMDB-21247: A 2.8 Angstrom Cryo-EM Structure of a Glycoprotein B-Neutralizing... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21247 | |||||||||||||||
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Title | A 2.8 Angstrom Cryo-EM Structure of a Glycoprotein B-Neutralizing Antibody Complex Reveals a Critical Domain for Herpesvirus Fusion Initiation | |||||||||||||||
![]() | Varicella zoster virus human neutralizing antibody, 93k, in complex with native gB | |||||||||||||||
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Function / homology | ![]() host cell Golgi membrane / host cell endosome membrane / membrane => GO:0016020 / symbiont entry into host cell / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||||||||
![]() | Oliver SL | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation. Authors: Stefan L Oliver / Yi Xing / Dong-Hua Chen / Soung Hun Roh / Grigore D Pintilie / David A Bushnell / Marvin H Sommer / Edward Yang / Andrea Carfi / Wah Chiu / Ann M Arvin / ![]() ![]() Abstract: Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells ...Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells to form polykaryocytes in infected tissues. The conserved glycoproteins, gB, gH and gL, are the core functional proteins of the herpesvirus fusion complex. gB serves as the primary fusogen via its fusion loops, but functions for the remaining gB domains remain unexplained. As a pathway for biological discovery of domain function, our approach used structure-based analysis of the viral fusogen together with a neutralizing antibody. We report here a 2.8 Å cryogenic-electron microscopy structure of native gB recovered from VZV-infected cells, in complex with a human monoclonal antibody, 93k. This high-resolution structure guided targeted mutagenesis at the gB-93k interface, providing compelling evidence that a domain spatially distant from the gB fusion loops is critical for herpesvirus fusion, revealing a potential new target for antiviral therapies. | |||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 202.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.5 KB 20.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.5 KB | Display | ![]() |
Images | ![]() | 170.1 KB | ||
Others | ![]() ![]() | 171.1 MB 171.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 649 KB | Display | ![]() |
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Full document | ![]() | 648.6 KB | Display | |
Data in XML | ![]() | 21 KB | Display | |
Data in CIF | ![]() | 27.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6vn1MC ![]() 6vlkC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Varicella zoster virus human neutralizing antibody, 93k, in complex with native gB | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: half map 1
File | emd_21247_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_21247_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Varicella zoster virus glycoprotein B in complex with Fab fragmen...
Entire | Name: Varicella zoster virus glycoprotein B in complex with Fab fragments derived from human monoclonal antibody 93k |
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Components |
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-Supramolecule #1: Varicella zoster virus glycoprotein B in complex with Fab fragmen...
Supramolecule | Name: Varicella zoster virus glycoprotein B in complex with Fab fragments derived from human monoclonal antibody 93k type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Experimental: 750 KDa |
-Supramolecule #2: human monoclonal antibody 93k Fab
Supramolecule | Name: human monoclonal antibody 93k Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: Varicella zoster virus glycoprotein B
Supramolecule | Name: Varicella zoster virus glycoprotein B / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Human monoclonal antibody 93k variable light chain
Macromolecule | Name: Human monoclonal antibody 93k variable light chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.826245 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIQMTQSPST LSASVGDRVT ITCRASQTIS TWLAWYQQTP RKAPKLMIYK ASILENGVPS RFSGSGSGTE FTLTISSLQP EDFATYYCQ QYKSYPWTFG QGTKVEI |
-Macromolecule #2: Human monoclonal antibody 93k variable heavy chain
Macromolecule | Name: Human monoclonal antibody 93k variable heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.658357 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS NFAISWVRQA PGQGLEWMGR IMPLFVTSTY AQKFQGRVTI SADASTSTAY MELSSLRSD DTAMYYCARD ITAPGAAPTP LNFYGMDVWG QGTTVTVSS |
-Macromolecule #3: Envelope glycoprotein B
Macromolecule | Name: Envelope glycoprotein B / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: HHV-3, Varicella zoster virus, Human alphaherpesvirus 3 |
Molecular weight | Theoretical: 105.50232 KDa |
Sequence | String: MSPCGYYSKW RNRDRPEYRR NLRFRRFFSS IHPNAAAGSG FNGPGVFITS VTGVWLCFLC IFSMFVTAVV SVSPSSFYES LQVEPTQSE DITRSAHLGD GDEIREAIHK SQDAETKPTF YVCPPPTGST IVRLEPPRTC PDYHLGKNFT EGIAVVYKEN I AAYKFKAT ...String: MSPCGYYSKW RNRDRPEYRR NLRFRRFFSS IHPNAAAGSG FNGPGVFITS VTGVWLCFLC IFSMFVTAVV SVSPSSFYES LQVEPTQSE DITRSAHLGD GDEIREAIHK SQDAETKPTF YVCPPPTGST IVRLEPPRTC PDYHLGKNFT EGIAVVYKEN I AAYKFKAT VYYKDVIVST AWAGSSYTQI TNRYADRVPI PVSEITDTID KFGKCSSKAT YVRNNHKVEA FNEDKNPQDM PL IASKYNS VGSKAWHTTN DTYMVAGTPG TYRTGTSVNC IIEEVEARSI FPYDSFGLST GDIIYMSPFF GLRDGAYREH SNY AMDRFH QFEGYRQRDL DTRALLEPAA RNFLVTPHLT VGWNWKPKRT EVCSLVKWRE VEDVVRDEYA HNFRFTMKTL STTF ISETN EFNLNQIHLS QCVKEEARAI INRIYTTRYN SSHVRTGDIQ TYLARGGFVV VFQPLLSNSL ARLYLQELVR ENTNH SPQK HPTRNTRSRR SVPVELRANR TITTTSSVEF AMLQFTYDHI QEHVNEMLAR ISSSWCQLQN RERALWSGLF PINPSA LAS TILDQRVKAR ILGDVISVSN CPELGSDTRI ILQNSMRVSG STTRCYSRPL ISIVSLNGSG TVEGQLGTDN ELIMSRD LL EPCVANHKRY FLFGHHYVYY EDYRYVREIA VHDVGMISTY VDLNLTLLKD REFMPLRVYT RDELRDTGLL DYSEIQRR N QMHSLRFYDI DKVVQYDSGT AIMQGMAQFF QGLGTAGQAV GHVVLGATGA LLSTVHGFTT FLSNPFGALA VGLLVLAGL VAAFFAYRYV LKLKTSPMKA LYPLTTKGLK QLPEGMDPFA EKPNATDTPI EEIGDSQNTE PSVNSGFDPD KFREAQEMIK YMTLVSAAE RQESKARKKN KTSALLTSRL TGLALRNRRG YSRVRTENVT GV |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 98 % / Chamber temperature: 298 K / Instrument: LEICA EM GP |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 4 / Number real images: 11283 / Average exposure time: 12.0 sec. / Average electron dose: 7.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |