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PDBsum entry 1kg0

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protein Protein-protein interface(s) links
Viral protein/immune system PDB id
1kg0
Jmol
Contents
Protein chains
180 a.a. *
188 a.a. *
13 a.a. *
136 a.a. *
Waters ×616
* Residue conservation analysis
PDB id:
1kg0
Name: Viral protein/immune system
Title: Structure of the epstein-barr virus gp42 protein bound to the mhc class ii receptor hla-dr1
Structure: Mhc class ii receptor hla-dr1. Chain: a. Fragment: alpha chain, extracellular domain. Engineered: yes. Mhc class ii receptor hla-dr1. Chain: b. Fragment: beta chain, extracellular domain. Engineered: yes. Hemagglutinin ha peptide.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide derived from influenza hemagglutinin sequence. Human herpesvirus 4.
Biol. unit: Tetramer (from PQS)
Resolution:
2.65Å     R-factor:   0.221     R-free:   0.247
Authors: M.M.Mullen,K.M.Haan,R.Longnecker,T.S.Jardetzky
Key ref:
M.M.Mullen et al. (2002). Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1. Mol Cell, 9, 375-385. PubMed id: 11864610 DOI: 10.1016/S1097-2765(02)00465-3
Date:
25-Nov-01     Release date:   27-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
Seq:
Struc:
254 a.a.
180 a.a.
Protein chain
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
Seq:
Struc:
266 a.a.
188 a.a.
Protein chain
No UniProt id for this chain
Struc: 13 a.a.
Protein chain
Pfam   ArchSchema ?
P03205  (GP42_EBVB9) -  Glycoprotein 42
Seq:
Struc:
223 a.a.
136 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 
  Biochemical function     carbohydrate binding     1 term  

 

 
DOI no: 10.1016/S1097-2765(02)00465-3 Mol Cell 9:375-385 (2002)
PubMed id: 11864610  
 
 
Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1.
M.M.Mullen, K.M.Haan, R.Longnecker, T.S.Jardetzky.
 
  ABSTRACT  
 
Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Interactions between gp42 and HLA-DR1(A) Ribbon diagram of the gp42:DR1 complex. gp42 is shown in red, DR1:HA in blue. The N-terminal region of gp42 forms a two-stranded, antiparallel β sheet with a crystallographically related symmetry mate.(B) Interactions formed by DR1 Eβ46 with gp42 residues. The gp42 chain is shown in red and DR1 in blue. Eβ46 forms a salt bridge (R220) and a hydrogen bond (Y107) across the interface, and single point mutations of Eβ46 have been shown to affect EBV entry and gp42 binding.(C) Interactions formed by DR1 Rβ72 with gp42 residues. Chains are colored as in (B). Rβ72 interacts primarily with the backbone atoms of the turn before the first β strand of the gp42 CTLD, including residues 104–107 and with the side chain of Y107. gp42 residues T104 and Y107 interact with both Eβ46 and Rβ72.
Figure 5.
Figure 5. Hydrophobic Character of the gp42 Canonical Ligand Binding Pocket(A) The gp42 structure reveals that a number of surface-exposed aromatic and hydrophobic residues line the putative ligand binding site. Aromatic residues F188, F198, F210, and Y185 are exposed at surface loops lining this site, with Y194 located at the base of the site. In addition, aliphatic residues V184, I159, I187, V201, and L211 contribute to additional hydrophobic character of the surface loops.(B) Surface representation of the gp42:DR1 complex showing the location of the aromatic and hydrophobic residues in (A). The putative binding site forms a broad and shallow groove that is oriented up and away from the MHC class II molecule, potentially directed away from the target cell membrane and toward the virus surface.(C) Hydrophobic surface patches identified by the program Quilt (Lijnzaad et al., 1996). Quilt was used to analyze the gp42 monomer, and the two largest hydrophobic patches are displayed. Atoms contributing to the largest hydrophobic patch ( vert, similar 620 Å^2) are shown in red. Atoms contributing to the second largest patch ( vert, similar 396 Å^2) are shown in blue. The top two hydrophobic patches define two of the three sides to the canonical binding site surface in gp42.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2002, 9, 375-385) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21478902 S.A.Connolly, J.O.Jackson, T.S.Jardetzky, and R.Longnecker (2011).
Fusing structure and function: a structural view of the herpesvirus entry machinery.
  Nat Rev Microbiol, 9, 369-381.  
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
20032175 H.P.Su, K.Singh, A.G.Gittis, and D.N.Garboczi (2010).
The structure of the poxvirus A33 protein reveals a dimer of unique C-type lectin-like domains.
  J Virol, 84, 2502-2510.
PDB code: 3k7b
20162447 P.L.Shaw, A.N.Kirschner, T.S.Jardetzky, and R.Longnecker (2010).
Characteristics of Epstein-Barr virus envelope protein gp42.
  Virus Genes, 40, 307-319.  
20178121 T.E.Quan, R.M.Roman, B.J.Rudenga, V.M.Holers, and J.E.Craft (2010).
Epstein-Barr virus promotes interferon-alpha production by plasmacytoid dendritic cells.
  Arthritis Rheum, 62, 1693-1701.  
19457993 A.E.Plate, J.Smajlović, T.S.Jardetzky, and R.Longnecker (2009).
Functional analysis of glycoprotein L (gL) from rhesus lymphocryptovirus in Epstein-Barr virus-mediated cell fusion indicates a direct role of gL in gB-induced membrane fusion.
  J Virol, 83, 7678-7689.  
19217393 A.N.Kirschner, J.Sorem, R.Longnecker, and T.S.Jardetzky (2009).
Structure of Epstein-Barr virus glycoprotein 42 suggests a mechanism for triggering receptor-activated virus entry.
  Structure, 17, 223-233.
PDB code: 3fd4
19217384 E.E.Heldwein (2009).
Entry of herpesviruses into cells: more than one way to pull the trigger.
  Structure, 17, 147-149.  
19369343 J.Sorem, T.S.Jardetzky, and R.Longnecker (2009).
Cleavage and secretion of Epstein-Barr virus glycoprotein 42 promote membrane fusion with B lymphocytes.
  J Virol, 83, 6664-6672.  
19196955 M.Backovic, R.Longnecker, and T.S.Jardetzky (2009).
Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B.
  Proc Natl Acad Sci U S A, 106, 2880-2885.
PDB code: 3fvc
19624613 R.Kelsch, T.M.Binder, H.A.Elsner, T.H.Eiermann, and W.Sibrowski (2009).
An HLA-DR11/DQ3 haplotype with a DRB1*0301 sequence motif in the third hypervariable region of the HLA-DR beta-1 chain: molecular and serological analysis of its generation in a European Caucasian family.
  Tissue Antigens, 74, 330-335.  
19342221 T.Stehle, and J.M.Casasnovas (2009).
Specificity switching in virus-receptor complexes.
  Curr Opin Struct Biol, 19, 181-188.  
17581996 A.N.Kirschner, A.S.Lowrey, R.Longnecker, and T.S.Jardetzky (2007).
Binding-site interactions between Epstein-Barr virus fusion proteins gp42 and gH/gL reveal a peptide that inhibits both epithelial and B-cell membrane fusion.
  J Virol, 81, 9216-9229.  
17925391 K.A.Young, X.S.Chen, V.M.Holers, and J.P.Hannan (2007).
Isolating the Epstein-Barr virus gp350/220 binding site on complement receptor type 2 (CR2/CD21).
  J Biol Chem, 282, 36614-36625.  
17459936 L.M.Hutt-Fletcher (2007).
Epstein-Barr virus entry.
  J Virol, 81, 7825-7832.  
17207708 R.J.Duquesnoy, and M.Askar (2007).
HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP.
  Hum Immunol, 68, 12-25.  
16973550 A.N.Kirschner, J.Omerovic, B.Popov, R.Longnecker, and T.S.Jardetzky (2006).
Soluble Epstein-Barr virus glycoproteins gH, gL, and gp42 form a 1:1:1 stable complex that acts like soluble gp42 in B-cell fusion but not in epithelial cell fusion.
  J Virol, 80, 9444-9454.  
17072314 G.Szakonyi, M.G.Klein, J.P.Hannan, K.A.Young, R.Z.Ma, R.Asokan, V.M.Holers, and X.S.Chen (2006).
Structure of the Epstein-Barr virus major envelope glycoprotein.
  Nat Struct Mol Biol, 13, 996.
PDB code: 2h6o
17001105 N.Tarbouriech, M.Buisson, T.Géoui, S.Daenke, S.Cusack, and W.P.Burmeister (2006).
Structural genomics of the Epstein-Barr virus.
  Acta Crystallogr D Biol Crystallogr, 62, 1276-1285.  
16474129 T.Gianni, A.Piccoli, C.Bertucci, and G.Campadelli-Fiume (2006).
Heptad repeat 2 in herpes simplex virus 1 gH interacts with heptad repeat 1 and is critical for virus entry and fusion.
  J Virol, 80, 2216-2224.  
16336259 A.N.Zelensky, and J.E.Gready (2005).
The C-type lectin-like domain superfamily.
  FEBS J, 272, 6179-6217.  
16292345 C.Krummenacher, V.M.Supekar, J.C.Whitbeck, E.Lazear, S.A.Connolly, R.J.Eisenberg, G.H.Cohen, D.C.Wiley, and A.Carfí (2005).
Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry.
  EMBO J, 24, 4144-4153.
PDB codes: 2c36 2c3a
16160168 J.Omerović, L.Lev, and R.Longnecker (2005).
The amino terminus of Epstein-Barr virus glycoprotein gH is important for fusion with epithelial and B cells.
  J Virol, 79, 12408-12415.  
15613312 M.E.Ressing, D.van Leeuwen, F.A.Verreck, S.Keating, R.Gomez, K.L.Franken, T.H.Ottenhoff, M.Spriggs, T.N.Schumacher, L.M.Hutt-Fletcher, M.Rowe, and E.J.Wiertz (2005).
Epstein-Barr virus gp42 is posttranslationally modified to produce soluble gp42 that mediates HLA class II immune evasion.
  J Virol, 79, 841-852.  
15073366 A.E.Smith, and A.Helenius (2004).
How viruses enter animal cells.
  Science, 304, 237-242.  
15140992 A.L.Silva, J.Omerovic, T.S.Jardetzky, and R.Longnecker (2004).
Mutational analyses of Epstein-Barr virus glycoprotein 42 reveal functional domains not involved in receptor binding but required for membrane fusion.
  J Virol, 78, 5946-5956.  
14748001 H.D.Schafroth, and C.A.Floudas (2004).
Predicting peptide binding to MHC pockets via molecular modeling, implicit solvation, and global optimization.
  Proteins, 54, 534-556.  
14555655 R.C.Hillig, M.Hülsmeyer, W.Saenger, K.Welfle, R.Misselwitz, H.Welfle, C.Kozerski, A.Volz, B.Uchanska-Ziegler, and A.Ziegler (2004).
Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.
  J Biol Chem, 279, 652-663.
PDB code: 1jgd
15507614 T.Gianni, G.Campadelli-Fiume, and L.Menotti (2004).
Entry of herpes simplex virus mediated by chimeric forms of nectin1 retargeted to endosomes or to lipid rafts occurs through acidic endosomes.
  J Virol, 78, 12268-12276.  
12740374 I.Potolicchio, L.Santambrogio, and J.L.Strominger (2003).
Molecular interaction and enzymatic activity of macrophage migration inhibitory factor with immunorelevant peptides.
  J Biol Chem, 278, 30889-30895.  
14691549 J.E.Slansky (2003).
Antigen-specific T cells: analyses of the needles in the haystack.
  PLoS Biol, 1, E78.  
14504389 M.E.Ressing, D.van Leeuwen, F.A.Verreck, R.Gomez, B.Heemskerk, M.Toebes, M.M.Mullen, T.S.Jardetzky, R.Longnecker, M.W.Schilham, T.H.Ottenhoff, J.Neefjes, T.N.Schumacher, L.M.Hutt-Fletcher, and E.J.Wiertz (2003).
Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition.
  Proc Natl Acad Sci U S A, 100, 11583-11588.  
12805465 M.P.McShane, M.M.Mullen, K.M.Haan, T.S.Jardetzky, and R.Longnecker (2003).
Mutational analysis of the HLA class II interaction with Epstein-Barr virus glycoprotein 42.
  J Virol, 77, 7655-7662.  
12970403 P.G.Spear, and R.Longnecker (2003).
Herpesvirus entry: an update.
  J Virol, 77, 10179-10185.  
12952957 Z.Zavala-Ruiz, E.J.Sundberg, J.D.Stone, D.B.DeOliveira, I.C.Chan, J.Svendsen, R.A.Mariuzza, and L.J.Stern (2003).
Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1.
  J Biol Chem, 278, 44904-44912.
PDB code: 1pyw
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 code is shown on the right.