1kg0 Citations

Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1.

Mol. Cell 9 375-85 (2002)
Cited: 80 times
EuropePMC logo PMID: 11864610

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.

Articles - 1kg0 mentioned but not cited (6)

  1. Re-Directing CD4(+) T Cell Responses with the Flanking Residues of MHC Class II-Bound Peptides: The Core is Not Enough. Holland CJ, Cole DK, Godkin A. Front Immunol 4 172 (2013)
  2. Chronic Beryllium Disease: revealing the role of beryllium ion and small peptides binding to HLA-DP2. Petukh M, Wu B, Stefl S, Smith N, Hyde-Volpe D, Wang L, Alexov E. PLoS ONE 9 e111604 (2014)
  3. An effective and effecient peptide binding prediction approach for a broad set of HLA-DR molecules based on ordered weighted averaging of binding pocket profiles. Shen WJ, Zhang S, Wong HS. Proteome Sci 11 S15 (2013)
  4. Overproduction, purification and preliminary crystallographic analysis of the carbohydrate-recognition domain of human langerin. Thépaut M, Vivès C, Pompidor G, Kahn R, Fieschi F. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 115-118 (2008)
  5. An automated framework for understanding structural variations in the binding grooves of MHC class II molecules. Yeturu K, Utriainen T, Kemp GJ, Chandra N. BMC Bioinformatics 11 Suppl 1 S55 (2010)
  6. HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells. Li Q, Bu W, Gabriel E, Aguilar F, Hoshino Y, Miyadera H, Hess C, Hornung RL, Roy A, Cohen JI. JCI Insight 2 e85687 (2017)


Reviews citing this publication (30)

  1. The C-type lectin-like domain superfamily. Zelensky AN, Gready JE. FEBS J. 272 6179-6217 (2005)
  2. Herpesvirus entry: an update. Spear PG, Longnecker R. J. Virol. 77 10179-10185 (2003)
  3. Herpes virus fusion and entry: a story with many characters. Eisenberg RJ, Atanasiu D, Cairns TM, Gallagher JR, Krummenacher C, Cohen GH. Viruses 4 800-832 (2012)
  4. Epstein-Barr virus entry. Hutt-Fletcher LM. J. Virol. 81 7825-7832 (2007)
  5. Stuck in the middle: structural insights into the role of the gH/gL heterodimer in herpesvirus entry. Stampfer SD, Heldwein EE. Curr Opin Virol 3 13-19 (2013)
  6. Specificity switching in virus-receptor complexes. Stehle T, Casasnovas JM. Curr. Opin. Struct. Biol. 19 181-188 (2009)
  7. Herpesviruses placating the unwilling host: manipulation of the MHC class II antigen presentation pathway. Zuo J, Rowe M. Viruses 4 1335-1353 (2012)
  8. The T cell antigen receptor: the Swiss army knife of the immune system. Attaf M, Legut M, Cole DK, Sewell AK. Clin. Exp. Immunol. 181 1-18 (2015)
  9. Antigen-specific T cells: analyses of the needles in the haystack. Slansky JE. PLoS Biol. 1 E78 (2003)
  10. Epstein Barr virus entry; kissing and conjugation. Shannon-Lowe C, Rowe M. Curr Opin Virol 4 78-84 (2014)
  11. Herpesvirus gB: A Finely Tuned Fusion Machine. Cooper RS, Heldwein EE. Viruses 7 6552-6569 (2015)
  12. Epstein-Barr virus infection mechanisms. Chesnokova LS, Hutt-Fletcher LM. Chin J Cancer 33 545-548 (2014)
  13. Structural and Mechanistic Insights into the Tropism of Epstein-Barr Virus. Möhl BS, Chen J, Sathiyamoorthy K, Jardetzky TS, Longnecker R. Mol. Cells 39 286-291 (2016)
  14. Giving CD4+ T cells the slip: viral interference with MHC class II-restricted antigen processing and presentation. Forsyth KS, Eisenlohr LC. Curr. Opin. Immunol. 40 123-129 (2016)
  15. Recent advances in understanding Epstein-Barr virus. Stanfield BA, Luftig MA. F1000Res 6 386 (2017)
  16. Recent advances in understanding Epstein-Barr virus. Stanfield BA, Luftig MA. F1000Res 6 386 (2017)
  17. Structural and Mechanistic Insights into the Tropism of Epstein-Barr Virus. Möhl BS, Chen J, Sathiyamoorthy K, Jardetzky TS, Longnecker R. Mol. Cells 39 286-291 (2016)
  18. Giving CD4+ T cells the slip: viral interference with MHC class II-restricted antigen processing and presentation. Forsyth KS, Eisenlohr LC. Curr. Opin. Immunol. 40 123-129 (2016)
  19. The T cell antigen receptor: the Swiss army knife of the immune system. Attaf M, Legut M, Cole DK, Sewell AK. Clin. Exp. Immunol. 181 1-18 (2015)
  20. Herpesvirus gB: A Finely Tuned Fusion Machine. Cooper RS, Heldwein EE. Viruses 7 6552-6569 (2015)
  21. Epstein Barr virus entry; kissing and conjugation. Shannon-Lowe C, Rowe M. Curr Opin Virol 4 78-84 (2014)
  22. Epstein-Barr virus infection mechanisms. Chesnokova LS, Hutt-Fletcher LM. Chin J Cancer 33 545-548 (2014)
  23. Stuck in the middle: structural insights into the role of the gH/gL heterodimer in herpesvirus entry. Stampfer SD, Heldwein EE. Curr Opin Virol 3 13-19 (2013)
  24. Herpes virus fusion and entry: a story with many characters. Eisenberg RJ, Atanasiu D, Cairns TM, Gallagher JR, Krummenacher C, Cohen GH. Viruses 4 800-832 (2012)
  25. Herpesviruses placating the unwilling host: manipulation of the MHC class II antigen presentation pathway. Zuo J, Rowe M. Viruses 4 1335-1353 (2012)
  26. Specificity switching in virus-receptor complexes. Stehle T, Casasnovas JM. Curr. Opin. Struct. Biol. 19 181-188 (2009)
  27. Epstein-Barr virus entry. Hutt-Fletcher LM. J. Virol. 81 7825-7832 (2007)
  28. The C-type lectin-like domain superfamily. Zelensky AN, Gready JE. FEBS J. 272 6179-6217 (2005)
  29. Herpesvirus entry: an update. Spear PG, Longnecker R. J. Virol. 77 10179-10185 (2003)
  30. Antigen-specific T cells: analyses of the needles in the haystack. Slansky JE. PLoS Biol. 1 E78 (2003)

Articles citing this publication (44)

  1. Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. Krummenacher C, Supekar VM, Whitbeck JC, Lazear E, Connolly SA, Eisenberg RJ, Cohen GH, Wiley DC, Carfí A. EMBO J. 24 4144-4153 (2005)
  2. Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B. Backovic M, Longnecker R, Jardetzky TS. Proc. Natl. Acad. Sci. U.S.A. 106 2880-2885 (2009)
  3. Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex. Matsuura H, Kirschner AN, Longnecker R, Jardetzky TS. Proc. Natl. Acad. Sci. U.S.A. 107 22641-22646 (2010)
  4. Modulation of B-cell exosome proteins by gamma herpesvirus infection. Meckes DG, Gunawardena HP, Dekroon RM, Heaton PR, Edwards RH, Ozgur S, Griffith JD, Damania B, Raab-Traub N. Proc. Natl. Acad. Sci. U.S.A. 110 E2925-33 (2013)
  5. Entry of herpes simplex virus mediated by chimeric forms of nectin1 retargeted to endosomes or to lipid rafts occurs through acidic endosomes. Gianni T, Campadelli-Fiume G, Menotti L. J. Virol. 78 12268-12276 (2004)
  6. HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP. Duquesnoy RJ, Askar M. Hum. Immunol. 68 12-25 (2007)
  7. The amino terminus of Epstein-Barr virus glycoprotein gH is important for fusion with epithelial and B cells. Omerović J, Lev L, Longnecker R. J. Virol. 79 12408-12415 (2005)
  8. Epstein-Barr virus gp42 is posttranslationally modified to produce soluble gp42 that mediates HLA class II immune evasion. Ressing ME, van Leeuwen D, Verreck FA, Keating S, Gomez R, Franken KL, Ottenhoff TH, Spriggs M, Schumacher TN, Hutt-Fletcher LM, Rowe M, Wiertz EJ. J. Virol. 79 841-852 (2005)
  9. Crystal structure of reovirus attachment protein σ1 in complex with sialylated oligosaccharides. Reiter DM, Frierson JM, Halvorson EE, Kobayashi T, Dermody TS, Stehle T. PLoS Pathog. 7 e1002166 (2011)
  10. Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition. Ressing ME, van Leeuwen D, Verreck FA, Gomez R, Heemskerk B, Toebes M, Mullen MM, Jardetzky TS, Longnecker R, Schilham MW, Ottenhoff TH, Neefjes J, Schumacher TN, Hutt-Fletcher LM, Wiertz EJ. Proc. Natl. Acad. Sci. U.S.A. 100 11583-11588 (2003)
  11. Fusion of Epstein-Barr virus with epithelial cells can be triggered by αvβ5 in addition to αvβ6 and αvβ8, and integrin binding triggers a conformational change in glycoproteins gHgL. Chesnokova LS, Hutt-Fletcher LM. J. Virol. 85 13214-13223 (2011)
  12. 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. Kirschner AN, Omerovic J, Popov B, Longnecker R, Jardetzky TS. J. Virol. 80 9444-9454 (2006)
  13. Mutational analyses of Epstein-Barr virus glycoprotein 42 reveal functional domains not involved in receptor binding but required for membrane fusion. Silva AL, Omerovic J, Jardetzky TS, Longnecker R. J. Virol. 78 5946-5956 (2004)
  14. Heptad repeat 2 in herpes simplex virus 1 gH interacts with heptad repeat 1 and is critical for virus entry and fusion. Gianni T, Piccoli A, Bertucci C, Campadelli-Fiume G. J. Virol. 80 2216-2224 (2006)
  15. Structure of the Epstein-Barr virus major envelope glycoprotein. Szakonyi G, Klein MG, Hannan JP, Young KA, Ma RZ, Asokan R, Holers VM, Chen XS. Nat. Struct. Mol. Biol. 13 996-1001 (2006)
  16. Epstein-Barr virus promotes interferon-alpha production by plasmacytoid dendritic cells. Quan TE, Roman RM, Rudenga BJ, Holers VM, Craft JE. Arthritis Rheum. 62 1693-1701 (2010)
  17. 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. Kirschner AN, Lowrey AS, Longnecker R, Jardetzky TS. J. Virol. 81 9216-9229 (2007)
  18. αvβ6- and αvβ8-integrins serve as interchangeable receptors for HSV gH/gL to promote endocytosis and activation of membrane fusion. Gianni T, Salvioli S, Chesnokova LS, Hutt-Fletcher LM, Campadelli-Fiume G. PLoS Pathog. 9 e1003806 (2013)
  19. Structure of Epstein-Barr virus glycoprotein 42 suggests a mechanism for triggering receptor-activated virus entry. Kirschner AN, Sorem J, Longnecker R, Jardetzky TS. Structure 17 223-233 (2009)
  20. 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. Plate AE, Smajlović J, Jardetzky TS, Longnecker R. J. Virol. 83 7678-7689 (2009)
  21. Predicting peptide binding to MHC pockets via molecular modeling, implicit solvation, and global optimization. Schafroth HD, Floudas CA. Proteins 54 534-556 (2004)
  22. Cleavage and secretion of Epstein-Barr virus glycoprotein 42 promote membrane fusion with B lymphocytes. Sorem J, Jardetzky TS, Longnecker R. J. Virol. 83 6664-6672 (2009)
  23. Assembly and architecture of the EBV B cell entry triggering complex. Sathiyamoorthy K, Jiang J, Hu YX, Rowe CL, Möhl BS, Chen J, Jiang W, Mellins ED, Longnecker R, Zhou ZH, Jardetzky TS. PLoS Pathog. 10 e1004309 (2014)
  24. Mutational analysis of the HLA class II interaction with Epstein-Barr virus glycoprotein 42. McShane MP, Mullen MM, Haan KM, Jardetzky TS, Longnecker R. J. Virol. 77 7655-7662 (2003)
  25. A novel bat herpesvirus encodes homologues of major histocompatibility complex classes I and II, C-type lectin, and a unique family of immune-related genes. Zhang H, Todd S, Tachedjian M, Barr JA, Luo M, Yu M, Marsh GA, Crameri G, Wang LF. J. Virol. 86 8014-8030 (2012)
  26. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells. Wang HB, Zhang H, Zhang JP, Li Y, Zhao B, Feng GK, Du Y, Xiong D, Zhong Q, Liu WL, Du H, Li MZ, Huang WL, Tsao SW, Hutt-Fletcher L, Zeng YX, Kieff E, Zeng MS. Nat Commun 6 6240 (2015)
  27. The structure of the poxvirus A33 protein reveals a dimer of unique C-type lectin-like domains. Su HP, Singh K, Gittis AG, Garboczi DN. J. Virol. 84 2502-2510 (2010)
  28. Mapping the N-terminal residues of Epstein-Barr virus gp42 that bind gH/gL by using fluorescence polarization and cell-based fusion assays. Liu F, Marquardt G, Kirschner AN, Longnecker R, Jardetzky TS. J. Virol. 84 10375-10385 (2010)
  29. Analysis of a neutralizing antibody for human herpesvirus 6B reveals a role for glycoprotein Q1 in viral entry. Kawabata A, Oyaizu H, Maeki T, Tang H, Yamanishi K, Mori Y. J. Virol. 85 12962-12971 (2011)
  30. Characteristics of Epstein-Barr virus envelope protein gp42. Shaw PL, Kirschner AN, Jardetzky TS, Longnecker R. Virus Genes 40 307-319 (2010)
  31. A soluble form of Epstein-Barr virus gH/gL inhibits EBV-induced membrane fusion and does not function in fusion. Rowe CL, Connolly SA, Chen J, Jardetzky TS, Longnecker R. Virology 436 118-126 (2013)
  32. The Epstein-Barr virus (EBV) glycoprotein B cytoplasmic C-terminal tail domain regulates the energy requirement for EBV-induced membrane fusion. Chen J, Zhang X, Jardetzky TS, Longnecker R. J. Virol. 88 11686-11695 (2014)
  33. Biophysical investigations of complement receptor 2 (CD21 and CR2)-ligand interactions reveal amino acid contacts unique to each receptor-ligand pair. Kovacs JM, Hannan JP, Eisenmesser EZ, Holers VM. J. Biol. Chem. 285 27251-27258 (2010)
  34. Dissociation of HSV gL from gH by αvβ6- or αvβ8-integrin promotes gH activation and virus entry. Gianni T, Massaro R, Campadelli-Fiume G. Proc. Natl. Acad. Sci. U.S.A. 112 E3901-10 (2015)
  35. Epstein-Barr and other viral mimicry of autoantigens, myelin and vitamin D-related proteins and of EIF2B, the cause of vanishing white matter disease: massive mimicry of multiple sclerosis relevant proteins by the Synechococcus phage. Carter CJ. Immunopharmacol Immunotoxicol 34 21-35 (2012)
  36. Investigation of the function of the putative self-association site of Epstein-Barr virus (EBV) glycoprotein 42 (gp42). Rowe CL, Matsuura H, Jardetzky TS, Longnecker R. Virology 415 122-131 (2011)
  37. Research Support, Non-U.S. Gov't Entry of herpesviruses into cells: more than one way to pull the trigger. Heldwein EE. Structure 17 147-149 (2009)
  38. Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of nasopharyngeal epithelial cells. Xiong D, Du Y, Wang HB, Zhao B, Zhang H, Li Y, Hu LJ, Cao JY, Zhong Q, Liu WL, Li MZ, Zhu XF, Tsao SW, Hutt-Fletcher LM, Song E, Zeng YX, Kieff E, Zeng MS. Proc. Natl. Acad. Sci. U.S.A. 112 11036-11041 (2015)
  39. Using proximity biotinylation to detect herpesvirus entry glycoprotein interactions: Limitations for integral membrane glycoproteins. Lajko M, Haddad AF, Robinson CA, Connolly SA. J. Virol. Methods 221 81-89 (2015)
  40. The conserved disulfide bond within domain II of Epstein-Barr virus gH has divergent roles in membrane fusion with epithelial cells and B cells. Möhl BS, Sathiyamoorthy K, Jardetzky TS, Longnecker R. J. Virol. 88 13570-13579 (2014)
  41. A gammaherpesvirus uses alternative splicing to regulate its tropism and its sensitivity to neutralization. Machiels B, Stevenson PG, Vanderplasschen A, Gillet L. PLoS Pathog. 9 e1003753 (2013)
  42. Membrane anchoring of Epstein-Barr virus gp42 inhibits fusion with B cells even with increased flexibility allowed by engineered spacers. Rowe CL, Chen J, Jardetzky TS, Longnecker R. MBio 6 (2015)
  43. Integrins as Herpesvirus Receptors and Mediators of the Host Signalosome. Campadelli-Fiume G, Collins-McMillen D, Gianni T, Yurochko AD. Annu Rev Virol 3 215-236 (2016)
  44. 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. Kelsch R, Binder TM, Elsner HA, Eiermann TH, Sibrowski W. Tissue Antigens 74 330-335 (2009)