PDBsum entry 3fvc

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Viral protein PDB id
Protein chain
559 a.a. *
NAG ×3
Waters ×9
* Residue conservation analysis
PDB id:
Name: Viral protein
Title: Crystal structure of a trimeric variant of the epstein-barr glycoprotein b
Structure: Glycoprotein gp110. Chain: a. Fragment: ectodomain. Synonym: gp115. Engineered: yes. Mutation: yes
Source: Human herpesvirus 4. Organism_taxid: 10377. Strain: b95. Gene: balf4, vglb_ebv. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
3.20Å     R-factor:   0.246     R-free:   0.283
Authors: M.Backovic
Key ref:
M.Backovic et al. (2009). Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B. Proc Natl Acad Sci U S A, 106, 2880-2885. PubMed id: 19196955 DOI: 10.1073/pnas.0810530106
15-Jan-09     Release date:   17-Mar-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P03188  (GB_EBVB9) -  Envelope glycoprotein B
857 a.a.
559 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 


DOI no: 10.1073/pnas.0810530106 Proc Natl Acad Sci U S A 106:2880-2885 (2009)
PubMed id: 19196955  
Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B.
M.Backovic, R.Longnecker, T.S.Jardetzky.
Epstein-Barr virus (EBV) is a herpesvirus that is associated with development of malignancies of lymphoid tissue. EBV infections are life-long and occur in >90% of the population. Herpesviruses enter host cells in a process that involves fusion of viral and cellular membranes. The fusion apparatus is comprised of envelope glycoprotein B (gB) and a heterodimeric complex made of glycoproteins H and L. Glycoprotein B is the most conserved envelope glycoprotein in human herpesviruses, and the structure of gB from Herpes simplex virus 1 (HSV-1) is available. Here, we report the crystal structure of the secreted EBV gB ectodomain, which forms 16-nm long spike-like trimers, structurally homologous to the postfusion trimers of the fusion protein G of vesicular stomatitis virus (VSV). Comparative structural analyses of EBV gB and VSV G, which has been solved in its pre and postfusion states, shed light on gB residues that may be involved in conformational changes and membrane fusion. Also, the EBV gB structure reveals that, despite the high sequence conservation of gB in herpesviruses, the relative orientations of individual domains, the surface charge distributions, and the structural details of EBV gB differ from the HSV-1 protein, indicating regions and residues that may have important roles in virus-specific entry.
  Selected figure(s)  
Figure 1.
Structure of the EBV gB Ectodomain. (A) The gB subunit is colored in blue to red, from N and to C terminus, which are labeled N and C, respectively. Numbers indicate N-glycosylated Asn residues, for which a single NAG molecule is modeled. FLs are marked and point in the same direction as the gB C terminus. The ectodomain shown here extends into a fairly hydrophobic, ≈40-residues long, stem region, and a single transmembrane domain, which were removed from the construct used for expression of the recombinant gB due to their high hydrophobicity. The 5 domains of EBV gB are indicated with roman numbers I to V, and are defined and labeled after nomenclature established for the HSV-1 gB ectodomain (Fig. S2 and Table S3). (B) The trimeric gB ectodomain is shown. The subunits are colored as magenta, cyan, and green. The subunit shown on A corresponds to the molecule shown in magenta. The subunits wrap around each other, forming extensive trimerization surfaces.
Figure 4.
Comparison of VSV G and EBV gB structures. (Upper) Postfusion conformations of VSV G and EBV gB. The structures are colored blue to red from their N to C termini. Domains of gB and G in their postfusion conformations have similar secondary structure topologies, although each of the gB domains is larger, and gB has an additional domain V, which is not present in G. Dashed arrows indicate the missing stem regions, and connect the C termini of the models (marked with letter C) with the expected transmembrane domain position. The prominent αF of VSV G, and the analogous αC of gB, are colored in yellow and indicated with arrows. Disulfide bridges of G, Cys^24-Cys^284, and gB, Cys^68-Cys^484, are marked and shown as magenta sticks, connecting the αF and αC, respectively, with the corresponding N-terminal segments (shown in blue). (Lower) The prefusion structure of VSV G and a theoretical model of the prefusion form of EBV gB. In the prefusion conformation of G, only domain III undergoes a significant refolding event (thus, marked as domain III*), which involves breaking of the long αF, whereas the other 3 domains relocate to a different position, but preserve their primary folds. Domain III of gB was modeled by using the domain III* of G as a guide. Dashed arrows represent the direction of stem regions in case of G, and domain V and stem regions for gB.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23292515 R.M.DuBois, M.C.Vaney, M.A.Tortorici, R.A.Kurdi, G.Barba-Spaeth, T.Krey, and F.A.Rey (2013).
Functional and evolutionary insight from the crystal structure of rubella virus protein E1.
  Nature, 493, 552-556.
PDB codes: 4adg 4adi 4adj 4b3v
21376360 A.E.Plate, J.J.Reimer, T.S.Jardetzky, and R.Longnecker (2011).
Mapping regions of Epstein-Barr virus (EBV) glycoprotein B (gB) important for fusion function with gH/gL.
  Virology, 413, 26-38.  
  21342525 L.I.Melnik, R.F.Garry, and C.A.Morris (2011).
Peptide inhibition of human cytomegalovirus infection.
  Virol J, 8, 76.  
20660204 A.L.Feire, R.M.Roy, K.Manley, and T.Compton (2010).
The glycoprotein B disintegrin-like domain binds beta 1 integrin to mediate cytomegalovirus entry.
  J Virol, 84, 10026-10037.  
  21122119 C.R.Siekavizza-Robles, S.J.Dollery, and A.V.Nicola (2010).
Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH.
  Virol J, 7, 352.  
21149717 H.Matsuura, A.N.Kirschner, R.Longnecker, and T.S.Jardetzky (2010).
Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex.
  Proc Natl Acad Sci U S A, 107, 22641-22646.
PDB code: 3phf
19939928 J.L.Silverman, S.Sharma, T.M.Cairns, and E.E.Heldwein (2010).
Fusion-deficient insertion mutants of herpes simplex virus type 1 glycoprotein B adopt the trimeric postfusion conformation.
  J Virol, 84, 2001-2012.  
21067549 J.Söllner, A.Heinzel, G.Summer, R.Fechete, L.Stipkovits, S.Szathmary, and B.Mayer (2010).
Concept and application of a computational vaccinology workflow.
  Immunome Res, 6, S7.  
21149698 M.Backovic, R.M.DuBois, J.J.Cockburn, A.J.Sharff, M.C.Vaney, H.Granzow, B.G.Klupp, G.Bricogne, T.C.Mettenleiter, and F.A.Rey (2010).
Structure of a core fragment of glycoprotein H from pseudorabies virus in complex with antibody.
  Proc Natl Acad Sci U S A, 107, 22635-22640.
PDB code: 2xqy
20427575 R.M.Markosyan, and F.S.Cohen (2010).
Negative potentials across biological membranes promote fusion by class II and class III viral proteins.
  Mol Biol Cell, 21, 2001-2012.  
19369321 B.P.Hannah, T.M.Cairns, F.C.Bender, J.C.Whitbeck, H.Lou, R.J.Eisenberg, and G.H.Cohen (2009).
Herpes simplex virus glycoprotein B associates with target membranes via its fusion loops.
  J Virol, 83, 6825-6836.  
  19765297 C.E.Garry, and R.F.Garry (2009).
Proteomics computational analyses suggest that the bornavirus glycoprotein is a class III viral fusion protein (gamma penetrene).
  Virol J, 6, 145.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.