|Entry||Database: EMDB / ID: EMD-22519|
|Title||The N-terminus of varicella-zoster virus glycoprotein B has a functional role in fusion|
|Sample||Monoclonal antibody 93k bound to varicella-zoster virus glycoprotein B:|
varicella-zoster virus glycoprotein B / monoclonal antibody 93k / nucleic-acidNucleic acid
|Biological species||Human alphaherpesvirus 3 (Varicella-zoster virus) / unidentified (others)|
|Method||single particle reconstruction / cryo EM / Resolution: 7.3 Å|
|Funding support|| United States, 6 items |
|Citation||Journal: PLoS Pathog / Year: 2021|
Title: The N-terminus of varicella-zoster virus glycoprotein B has a functional role in fusion.
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: Varicella-zoster virus (VZV) is a medically important alphaherpesvirus that induces fusion of the virion envelope and the cell membrane during entry, and between cells to form polykaryocytes within ...Varicella-zoster virus (VZV) is a medically important alphaherpesvirus that induces fusion of the virion envelope and the cell membrane during entry, and between cells to form polykaryocytes within infected tissues during pathogenesis. All members of the Herpesviridae, including VZV, have a conserved core fusion complex composed of glycoproteins, gB, gH and gL. The ectodomain of the primary fusogen, gB, has five domains, DI-V, of which DI contains the fusion loops needed for fusion function. We recently demonstrated that DIV is critical for fusion initiation, which was revealed by a 2.8Å structure of a VZV neutralizing mAb, 93k, bound to gB and mutagenesis of the gB-93k interface. To further assess the mechanism of mAb 93k neutralization, the binding site of a non-neutralizing mAb to gB, SG2, was compared to mAb 93k using single particle cryogenic electron microscopy (cryo-EM). The gB-SG2 interface partially overlapped with that of gB-93k but, unlike mAb 93k, mAb SG2 did not interact with the gB N-terminus, suggesting a potential role for the gB N-terminus in membrane fusion. The gB ectodomain structure in the absence of antibody was defined at near atomic resolution by single particle cryo-EM (3.9Å) of native, full-length gB purified from infected cells and by X-ray crystallography (2.4Å) of the transiently expressed ectodomain. Both structures revealed that the VZV gB N-terminus (aa72-114) was flexible based on the absence of visible structures in the cryo-EM or X-ray crystallography data but the presence of gB N-terminal peptides were confirmed by mass spectrometry. Notably, N-terminal residues 109KSQD112 were predicted to form a small α-helix and alanine substitution of these residues abolished cell-cell fusion in a virus-free assay. Importantly, transferring the 109AAAA112 mutation into the VZV genome significantly impaired viral propagation. These data establish a functional role for the gB N-terminus in membrane fusion broadly relevant to the Herpesviridae.
|Validation Report||Summary, Full report, XML, About validation report|
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_22519.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.283 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Monoclonal antibody 93k bound to varicella-zoster virus glycoprotein B
|Entire||Name: Monoclonal antibody 93k bound to varicella-zoster virus glycoprotein B|
Number of components: 4
-Component #1: protein, Monoclonal antibody 93k bound to varicella-zoster virus ...
|Protein||Name: Monoclonal antibody 93k bound to varicella-zoster virus glycoprotein B|
Recombinant expression: No
-Component #2: protein, varicella-zoster virus glycoprotein B
|Protein||Name: varicella-zoster virus glycoprotein B / Recombinant expression: No|
|Source||Species: Human alphaherpesvirus 3 (Varicella-zoster virus)|
-Component #3: protein, monoclonal antibody 93k
|Protein||Name: monoclonal antibody 93k / Recombinant expression: No|
|Source||Species: unidentified (others)|
-Component #4: nucleic-acid, Monoclonal antibody 93k bound to varicella-zoster v...
|nucleic acid||Name: Monoclonal antibody 93k bound to varicella-zoster virus glycoprotein B|
Class: OTHER / Structure: OTHER / Synthetic: No
Sequence: MSPCGYYSKW RNRDRPEYRR NLRFRRFFSS IHPNAAAGSG FNGPGVFITS VTGVWLCFLC IFSMFVTAVV SVSPSSFYES LQVEPTQSED ITRSAHLGDG DEIREAIHKS QDAETKPTFY VCPPPTGSTI VRLEPPRTCP DYHLGKNFTE GIAVVYKENI AAYKFKATVY ...Sequence:
MSPCGYYSKW RNRDRPEYRR NLRFRRFFSS IHPNAAAGSG FNGPGVFITS VTGVWLCFLC IFSMFVTAVV SVSPSSFYES LQVEPTQSED ITRSAHLGDG DEIREAIHKS QDAETKPTFY VCPPPTGSTI VRLEPPRTCP DYHLGKNFTE GIAVVYKENI AAYKFKATVY YKDVIVSTAW AGSSYTQITN RYADRVPIPV SEITDTIDKF GKCSSKATYV RNNHKVEAFN EDKNPQDMPL IASKYNSVGS KAWHTTNDTY MVAGTPGTYR TGTSVNCIIE EVEARSIFPY DSFGLSTGDI IYMSPFFGLR DGAYREHSNY AMDRFHQFEG YRQRDLDTRA LLEPAARNFL VTPHLTVGWN WKPKRTEVCS LVKWREVEDV VRDEYAHNFR FTMKTLSTTF ISETNEFNLN QIHLSQCVKE EARAIINRIY TTRYNSSHVR TGDIQTYLAR GGFVVVFQPL LSNSLARLYL QELVRENTNH SPQKHPTRNT RSRRSVPVEL RANRTITTTS SVEFAMLQFT YDHIQEHVNE MLARISSSWC QLQNRERALW SGLFPINPSA LASTILDQRV KARILGDVIS VSNCPELGSD TRIILQNSMR VSGSTTRCYS RPLISIVSLN GSGTVEGQLG TDNELIMSRD LLEPCVANHK RYFLFGHHYV YYEDYRYVRE IAVHDVGMIS TYVDLNLTLL KDREFMPLRV YTRDELRDTG LLDYSEIQRR NQMHSLRFYD IDKVVQYDSG TAIMQGMAQF FQGLGTAGQA VGHVVLGATG ALLSTVHGFT TFLSNPFGAL AVGLLVLAGL VAAFFAYRYV LKLKTSPMKA LYPLTTKGLK QLPEGMDPFA EKPNATDTPI EEIGDSQNTE PSVNSGFDPD KFREAQEMIK YMTLVSAAER QESKARKKNK TSALLTSRLT GLALRNRRGY SRVRTENVTG V
|Source||Species: Human alphaherpesvirus 3 (Varicella-zoster virus)|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||pH: 7.4|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Tecnai F20 / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI F20|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 7.8 e/Å2 / Illumination mode: OTHER|
|Lens||Imaging mode: OTHER|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 SUMMIT (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 39591|
|3D reconstruction||Resolution: 7.3 Å / Resolution method: FSC 0.143 CUT-OFF|
-Aug 12, 2020. New: Covid-19 info
New: Covid-19 info
Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data
-Mar 5, 2020. Novel coronavirus structure data
Novel coronavirus structure data
- International Committee on Taxonomy of Viruses (ICTV) defined the short name of the 2019 coronavirus as "SARS-CoV-2".
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 - nature microbiology
- In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Related info.:Yorodumi Speices / Aug 12, 2020. New: Covid-19 info
+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
- The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force. (see PDBe EMDB page)
- The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is "EMD"? / ID/Accession-code notation in Yorodumi/EM Navigator
+Jul 12, 2017. Major update of PDB
Major update of PDB
- wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
- In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.
+Jun 16, 2017. Omokage search with filter
Omokage search with filter
- Result of Omokage search can be filtered by keywords and the database types
Related info.:Omokage search
Thousand views of thousand structures
- Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
- This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi