Skip to main content

Advertisement

Log in

Identification of putative functional motifs in viral proteins essential for human cytomegalovirus DNA replication

  • Published:
Virus Genes Aims and scope Submit manuscript

Abstract

Six of the eleven genes essential for Human cytomegalovirus (HCMV) DNA synthesis have been analyzed for putative structural motifs that may have a significant functional role in DNA replication. The genes studied encode for the DNA polymerase accessory protein (UL44), single-stranded DNA binding protein (UL57), primase-helicase complex (UL70, UL102, and UL105), and the putative initiator protein (UL84). The full-length open reading frames of these genes were highly conserved between ten isolates with amino acid sequence identity of >97% for all genes. Using ScanProsite software from the Expert Protein Analysis System (ExPASy) proteomics server, we have mapped putative motifs throughout these HCMV replication genes. Interesting motifs identified include casein kinase-2 (CKII) phosphorylation sites, a microbodies signal motif in UL57, and an ATP binding site in the putative UL105 helicase. Our investigations have also elucidated motif-rich regions of the UL44 DNA polymerase accessory protein and identified cysteine motifs that have potential implications for UL57 and UL70 primase. Taken together, these findings provide insights to regions of these HCMV replication proteins that are important for post-translation modification, activation, and overall function, and this information can be utilized to target further research into these proteins and advance the development of novel antiviral agents that target these processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. M. Boeckh, W.G. Nichols, Blood 103, 2003–2008 (2004). doi:https://doi.org/10.1182/blood-2003-10-3616

    Article  CAS  Google Scholar 

  2. A. Dolan, C. Cunningham, R.D. Hector, A.F. Hassan-Walker, L. Lee, C. Addison et al., J. Gen. Virol. 85, 1301–1312 (2004). doi:https://doi.org/10.1099/vir.0.79888-0

    Article  CAS  Google Scholar 

  3. G.S. Pari, D.G. Anders, J. Virol. 67, 6979–6988 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  4. D.G. Anders, L.A. McCue, Intervirology 39, 378–388 (1996)

    Article  CAS  Google Scholar 

  5. A.C. Iskenderian, L. Huang, A. Reilly, R.M. Stenberg, D.G. Anders, J. Virol. 70, 383–392 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. M.S. Chee, A.T. Bankier, S. Beck, R. Bohni, C.M. Brown, R. Cerny et al., Curr. Top. Microbiol. Immunol. 154, 125–169 (1990)

    CAS  PubMed  Google Scholar 

  7. B.A. Appleton, A. Loregian, D.J. Filman, D.M. Coen, J.M. Hogle, Mol. Cell 15, 233–244 (2004). doi:https://doi.org/10.1016/j.molcel.2004.06.018

    Article  CAS  Google Scholar 

  8. A. Loregian, B.A. Appleton, J.M. Hogle, D.M. Coen, J. Virol. 78, 9084–9092 (2004). doi:https://doi.org/10.1128/JVI.78.17.9084-9092.2004

    Article  CAS  Google Scholar 

  9. B.A. Appleton, J. Brooks, A. Loregian, D.J. Filman, D.M. Coen, J.M. Hogle, J. Biol. Chem. 281, 5224–5232 (2006). doi:https://doi.org/10.1074/jbc.M506900200

    Article  CAS  Google Scholar 

  10. D.G. Anders, J.R. Kidd, W. Gibson, Virology 161, 579–588 (1987). doi:https://doi.org/10.1016/0042-6822(87)90154-1

    Article  CAS  Google Scholar 

  11. T.P. McMahon, D.G. Anders, Virus Res. 86, 39–52 (2002). doi:https://doi.org/10.1016/S0168-1702(02)00054-0

    Article  CAS  Google Scholar 

  12. S. Dracheva, E.V. Koonin, J.J. Crute, J. Biol. Chem. 270, 14148–14153 (1995). doi:https://doi.org/10.1074/jbc.270.23.14148

    Article  CAS  Google Scholar 

  13. D.K. Klinedinst, M.D. Challberg, J. Virol. 68, 3693–3701 (1994)

    CAS  PubMed  PubMed Central  Google Scholar 

  14. L. Zhu, S.K. Weller, J. Virol. 66, 469–479 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. R.T. Sarisky, G.S. Hayward, J. Virol. 70, 7398–7413 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Y. Xu, S.A. Cei, A. Rodriguez Huete, K.S. Colletti, G.S. Pari, J. Virol. 78, 11664–11677 (2004). doi:https://doi.org/10.1128/JVI.78.21.11664-11677.2004

    Article  CAS  Google Scholar 

  17. Y. Gao, K. Colletti, G.S. Pari, J. Virol. 82, 96–104 (2008). doi:https://doi.org/10.1128/JVI.01559-07

    Article  CAS  Google Scholar 

  18. P. Lischka, C. Rauh, R. Mueller, T. Stamminger, J. Virol. 80, 10274–10280 (2006). doi:https://doi.org/10.1128/JVI.00995-06

    Article  CAS  Google Scholar 

  19. M. Craxton, Methods 3, 20–24 (1991). doi:https://doi.org/10.1016/S1046-2023(05)80159-8

    Article  CAS  Google Scholar 

  20. J.D. Thompson, D.G. Higgins, T.J. Gibson, Nucleic Acids Res. 22, 4673–4680 (1994). doi:https://doi.org/10.1093/nar/22.22.4673

    Article  CAS  Google Scholar 

  21. J. Felsenstein, Cladistics 5, 164–166 (1989)

    Google Scholar 

  22. N. Hulo, A. Bairoch, V. Bulliard, L. Cerutti, E. De Castro, P.S. Langendijk-Genevaux et al., Nucleic Acids Res. 34, D227–D230 (2006). doi:https://doi.org/10.1093/nar/gkj063

    Article  CAS  Google Scholar 

  23. C.J. Sigrist, E. De Castro, P.S. Langendijk-Genevaux, V. Le Saux, A. Bairoch, N. Hulo, Bioinformatics 21, 4060–4066 (2005). doi:https://doi.org/10.1093/bioinformatics/bti614

    Article  CAS  Google Scholar 

  24. E. de Castro, C.J. Sigrist, A. Gattiker, V. Bulliard, P.S. Langendijk-Genevaux, E. Gasteiger et al., Nucleic Acids Res. 34, W362–W365 (2006). doi:https://doi.org/10.1093/nar/gkl124

    Article  Google Scholar 

  25. S.F. Altschul, T.L. Madden, A.A. Schäffer, J. Zhang, Z. Zhang, W. Miller et al., Nucleic Acids Res. 25, 3389–3402 (1997). doi:https://doi.org/10.1093/nar/25.17.3389

    Article  CAS  Google Scholar 

  26. G. Alvisi, D.A. Jans, J. Guo, L.A. Pinna, A. Ripalti, Traffic 6, 1002–1013 (2005). doi:https://doi.org/10.1111/j.1600-0854.2005.00331.x

    Article  CAS  Google Scholar 

  27. K.L. Graves-Woodward, J. Gottlieb, M.D. Challberg, S.K. Weller, J. Biol. Chem. 272, 4623–4630 (1997). doi:https://doi.org/10.1074/jbc.272.7.4623

    Article  CAS  Google Scholar 

  28. K.S. Colletti, Y. Xu, S.A. Cei, M. Tarrant, G.S. Pari, J. Virol. 78, 9203–9214 (2004). doi:https://doi.org/10.1128/JVI.78.17.9203-9214.2004

    Article  CAS  Google Scholar 

  29. M.I. Barrasa, N.Y. Harel, J.C. Alwine, J. Virol. 79, 1428–1437 (2005). doi:https://doi.org/10.1128/JVI.79.3.1428-1437.2005

    Article  CAS  Google Scholar 

  30. M.A. Jarvis, T.R. Jones, D.D. Drummond, P.P. Smith, W.J. Britt, J.A. Nelson, C.J. Baldick, J. Virol. 78, 285–293 (2004)

    Article  CAS  Google Scholar 

  31. M.T. Nogalski, J.P. Podduturi, I.B. DeMeritt, L.E. Milford, A.D. Yurochko, J. Virol. 81, 5305–5314 (2007). doi:https://doi.org/10.1128/JVI.02382-06

    Article  CAS  Google Scholar 

  32. K.L. Weiland, N.L. Oien, F. Homa, M.W. Wathen, Virus Res. 34, 191–206 (1994). doi:https://doi.org/10.1016/0168-1702(94)90124-4

    Article  CAS  Google Scholar 

  33. P.F. Ertl, K.L. Powell, J. Virol. 66, 4126–4133 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  34. R.O. Haynes, Cell 110, 673–687 (2002). doi:https://doi.org/10.1016/S0092-8674(02)00971-6

    Article  Google Scholar 

  35. L.C. Loh, D. Locke, R. Melnychuk, S. Laferte, Virology 272, 302–314 (2000). doi:https://doi.org/10.1006/viro.2000.0366

    Article  CAS  Google Scholar 

  36. Y.S. Wang, J.D. Hall, J. Virol. 64, 2082–2089 (1990)

    CAS  PubMed  PubMed Central  Google Scholar 

  37. K.J. Woycechowsky, R.T. Raines, Biochemistry 42, 5387–5394 (2003). doi:https://doi.org/10.1021/bi026993q

    Article  CAS  Google Scholar 

  38. S. Krishnaswamy, M.G. Rossmann, J. Mol. Biol. 211, 803–844 (1990). doi:https://doi.org/10.1016/0022-2836(90)90077-Y

    Article  CAS  Google Scholar 

  39. C.A. Smith, H.S. Toogood, H.M. Baker, R.M. Daniel, E.N. Baker, J. Mol. Biol. 294, 1027–1040 (1999). doi:https://doi.org/10.1006/jmbi.1999.3291

    Article  CAS  Google Scholar 

  40. U. Jakob, W. Muse, M. Eser, J.C. Bardwell, Cell 96, 341–352 (1999). doi:https://doi.org/10.1016/S0092-8674(00)80547-4

    Article  CAS  Google Scholar 

  41. N. Biswas, S.K. Weller, J. Biol. Chem. 274, 8068–8076 (1999). doi:https://doi.org/10.1074/jbc.274.12.8068

    Article  CAS  Google Scholar 

  42. S.F. Michael, V.J. Kilfoil, M.H. Schmidt, B.T. Amann, J.M. Berg, Proc. Natl. Acad. Sci. U.S.A. 89, 4796–4800 (1992). doi:https://doi.org/10.1073/pnas.89.11.4796

    Article  CAS  Google Scholar 

  43. J.E. Walker, M. Saraste, M.J. Runswick, N.J. Gay, EMBO J. 1, 945–951 (1982)

    Article  CAS  Google Scholar 

  44. P. Lischka, G. Sorg, M. Kann, M. Winkler, T. Stamminger, J. Virol. 77, 3734–3748 (2003). doi:https://doi.org/10.1128/JVI.77.6.3734-3748.2003

    Article  CAS  Google Scholar 

  45. K.S. Colletti, K.E. Smallenburg, Y. Xu, G.S. Pari, J. Virol. 81, 7077–7085 (2007). doi:https://doi.org/10.1128/JVI.00058-07

    Article  CAS  Google Scholar 

  46. K.S. Colletti, Y. Xu, I. Yamboliev, G.S. Pari, J. Biol. Chem. 280, 11955–11960 (2005). doi:https://doi.org/10.1074/jbc.C400603200

    Article  CAS  Google Scholar 

  47. L.A. Pinna, Biochim. Biophys. Acta 1054, 267–284 (1990)

    Article  CAS  Google Scholar 

  48. Y. Xu, K.S. Colletti, G.S. Pari, J. Virol. 76, 8931–8938 (2002). doi:https://doi.org/10.1128/JVI.76.17.8931-8938.2002

    Article  CAS  Google Scholar 

  49. Y.S. He, L. Xu, E.S. Huang, J. Virol. 66, 1098–1108 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  50. F. Meggio, L.A. Pinna, FASEB J. 17, 349–368 (2003). doi:https://doi.org/10.1096/fj.02-0473rev

    Article  CAS  Google Scholar 

  51. J.A. Smith, G.S. Pari, J. Virol. 69, 1734–1740 (1995)

    CAS  PubMed  PubMed Central  Google Scholar 

  52. J.A. Smith, S. Jairath, J.J. Cryte, G.S. Pari, Virology 220, 251–255 (1996). doi:https://doi.org/10.1006/viro.1996.0310

    Article  CAS  Google Scholar 

  53. D.G. Anders, W. Gibson, J. Virol. 62, 1364–1372 (1988)

    CAS  PubMed  PubMed Central  Google Scholar 

  54. J.E. Craighead, R.E. Kanich, J.D. Almeida, J. Virol. 10, 766–775 (1972)

    CAS  PubMed  PubMed Central  Google Scholar 

  55. B.H. Ruebner, T. Hirano, R. Slusser, J. Osborn, D.N. Medearis Jr., Am. J. Pathol. 48, 971–989 (1966)

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William D. Rawlinson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woon, HG., Scott, G.M., Yiu, K.L. et al. Identification of putative functional motifs in viral proteins essential for human cytomegalovirus DNA replication. Virus Genes 37, 193–202 (2008). https://doi.org/10.1007/s11262-008-0255-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11262-008-0255-8

Keywords

Navigation