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. 1988 Sep;85(18):6637–6641. doi: 10.1073/pnas.85.18.6637

Distinctive charge configurations in proteins of the Epstein-Barr virus and possible functions.

B E Blaisdell 1, S Karlin 1
PMCID: PMC282032  PMID: 2842782

Abstract

The protein products of several open reading frames (ORFs) of the Epstein-Barr virus (EBV) are remarkable in their distribution of charged residues. The nuclear antigen proteins EBNA1-EBNA4 of the EBV latent state contain separate significant clusters of charge of each sign. They (excepting EBNA4) also feature distinctive periodic charge patterns [e.g., (+, O)8, (O, -, -)7] and significant tandem repeats. None of the other ORFs (about 80) of the genome possess the conjunction of these properties. Only the protein encoded from BMLF1, the first immediate early transactivator protein, contains significant multiple charge clusters and periodic charge patterns. All proteins that contain significant repeats also contain at least one significant charge cluster of a single sign. These include EBNA5 and LYDMA produced during latency and BZLF1, whose expression terminates latency and initiates productive growth. It is reasonable to conclude that these aggregate significant charge configurations and repeats are important functionally for the latent existence and for the initiation of the lytic cycle and may be characteristic of these conditions. We discuss how large multimeric protein structures bound together by clusters of unlike charge may provide a mechanism for regulation of the expression of these proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arriza J. L., Weinberger C., Cerelli G., Glaser T. M., Handelin B. L., Housman D. E., Evans R. M. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987 Jul 17;237(4812):268–275. doi: 10.1126/science.3037703. [DOI] [PubMed] [Google Scholar]
  2. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  3. Beisel C., Tanner J., Matsuo T., Thorley-Lawson D., Kezdy F., Kieff E. Two major outer envelope glycoproteins of Epstein-Barr virus are encoded by the same gene. J Virol. 1985 Jun;54(3):665–674. doi: 10.1128/jvi.54.3.665-674.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bodescot M., Brison O., Perricaudet M. An Epstein-Barr virus transcription unit is at least 84 kilobases long. Nucleic Acids Res. 1986 Mar 25;14(6):2611–2620. doi: 10.1093/nar/14.6.2611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bodescot M., Perricaudet M., Farrell P. J. A promoter for the highly spliced EBNA family of RNAs of Epstein-Barr virus. J Virol. 1987 Nov;61(11):3424–3430. doi: 10.1128/jvi.61.11.3424-3430.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chevallier-Greco A., Manet E., Chavrier P., Mosnier C., Daillie J., Sergeant A. Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO J. 1986 Dec 1;5(12):3243–3249. doi: 10.1002/j.1460-2075.1986.tb04635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chou P. Y., Fasman G. D. Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. Biochemistry. 1974 Jan 15;13(2):211–222. doi: 10.1021/bi00699a001. [DOI] [PubMed] [Google Scholar]
  8. Countryman J., Jenson H., Seibl R., Wolf H., Miller G. Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency. J Virol. 1987 Dec;61(12):3672–3679. doi: 10.1128/jvi.61.12.3672-3679.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  10. Davison A. J., Taylor P. Genetic relations between varicella-zoster virus and Epstein-Barr virus. J Gen Virol. 1987 Apr;68(Pt 4):1067–1079. doi: 10.1099/0022-1317-68-4-1067. [DOI] [PubMed] [Google Scholar]
  11. Dillner J., Kallin B., Alexander H., Ernberg I., Uno M., Ono Y., Klein G., Lerner R. A. An Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6641–6645. doi: 10.1073/pnas.83.17.6641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fennewald S., van Santen V., Kieff E. Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein. J Virol. 1984 Aug;51(2):411–419. doi: 10.1128/jvi.51.2.411-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garcea R. L., Salunke D. M., Caspar D. L. Site-directed mutation affecting polyomavirus capsid self-assembly in vitro. Nature. 1987 Sep 3;329(6134):86–87. doi: 10.1038/329086a0. [DOI] [PubMed] [Google Scholar]
  14. Hennessy K., Kieff E. A second nuclear protein is encoded by Epstein-Barr virus in latent infection. Science. 1985 Mar 8;227(4691):1238–1240. doi: 10.1126/science.2983420. [DOI] [PubMed] [Google Scholar]
  15. Hennessy K., Wang F., Bushman E. W., Kieff E. Definitive identification of a member of the Epstein-Barr virus nuclear protein 3 family. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5693–5697. doi: 10.1073/pnas.83.15.5693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Karlin S., Blaisdell B. E. A model for the development of the tandem repeat units in the EBV ori-P region and a discussion of their possible function. J Mol Evol. 1987;25(3):215–229. doi: 10.1007/BF02100015. [DOI] [PubMed] [Google Scholar]
  17. Lieberman P. M., O'Hare P., Hayward G. S., Hayward S. D. Promiscuous trans activation of gene expression by an Epstein-Barr virus-encoded early nuclear protein. J Virol. 1986 Oct;60(1):140–148. doi: 10.1128/jvi.60.1.140-148.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Manet E., Chevallier A., Zhang C. X., Ooka T., Chavrier P., Daillie J. Construction and use of cDNA clones for the mapping and identification of Epstein-Barr virus early P3HR-1 mRNAs. J Virol. 1985 May;54(2):608–614. doi: 10.1128/jvi.54.2.608-614.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Milman G., Hwang E. S. Epstein-Barr virus nuclear antigen forms a complex that binds with high concentration dependence to a single DNA-binding site. J Virol. 1987 Feb;61(2):465–471. doi: 10.1128/jvi.61.2.465-471.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Noda M., Shimizu S., Tanabe T., Takai T., Kayano T., Ikeda T., Takahashi H., Nakayama H., Kanaoka Y., Minamino N. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature. 1984 Nov 8;312(5990):121–127. doi: 10.1038/312121a0. [DOI] [PubMed] [Google Scholar]
  21. Rawlins D. R., Milman G., Hayward S. D., Hayward G. S. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985 Oct;42(3):859–868. doi: 10.1016/0092-8674(85)90282-x. [DOI] [PubMed] [Google Scholar]
  22. Reisman D., Sugden B. trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol. 1986 Nov;6(11):3838–3846. doi: 10.1128/mcb.6.11.3838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reisman D., Yates J., Sugden B. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol. 1985 Aug;5(8):1822–1832. doi: 10.1128/mcb.5.8.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Richardson W. D., Roberts B. L., Smith A. E. Nuclear location signals in polyoma virus large-T. Cell. 1986 Jan 17;44(1):77–85. doi: 10.1016/0092-8674(86)90486-1. [DOI] [PubMed] [Google Scholar]
  25. Ricksten A., Kallin B., Alexander H., Dillner J., Fåhraeus R., Klein G., Lerner R., Rymo L. BamHI E region of the Epstein-Barr virus genome encodes three transformation-associated nuclear proteins. Proc Natl Acad Sci U S A. 1988 Feb;85(4):995–999. doi: 10.1073/pnas.85.4.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sample J., Hummel M., Braun D., Birkenbach M., Kieff E. Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5096–5100. doi: 10.1073/pnas.83.14.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Skare J., Farley J., Strominger J. L., Fresen K. O., Cho M. S., zur Hausen H. Transformation by Epstein-Barr virus requires DNA sequences in the region of BamHI fragments Y and H. J Virol. 1985 Aug;55(2):286–297. doi: 10.1128/jvi.55.2.286-297.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith A. E., Kalderon D., Roberts B. L., Colledge W. H., Edge M., Gillett P., Markham A., Paucha E., Richardson W. D. The nuclear location signal. Proc R Soc Lond B Biol Sci. 1985 Oct 22;226(1242):43–58. doi: 10.1098/rspb.1985.0078. [DOI] [PubMed] [Google Scholar]
  29. Spangler R., Bruner M., Dalie B., Harter M. L. Activation of adenovirus promoters by the adenovirus E1A protein in cell-free extracts. Science. 1987 Aug 28;237(4818):1044–1046. doi: 10.1126/science.2956686. [DOI] [PubMed] [Google Scholar]
  30. Speck S. H., Strominger J. L. Analysis of the transcript encoding the latent Epstein-Barr virus nuclear antigen I: a potentially polycistronic message generated by long-range splicing of several exons. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8305–8309. doi: 10.1073/pnas.82.24.8305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Suck D., Lahm A., Oefner C. Structure refined to 2A of a nicked DNA octanucleotide complex with DNase I. Nature. 1988 Mar 31;332(6163):464–468. doi: 10.1038/332464a0. [DOI] [PubMed] [Google Scholar]

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