Crystal Structure of the Gamma-2 Herpesvirus LANA DNA Binding Domain Identifies Charged Surface Residues Which Impact Viral Latency

PLoS Pathogens

Volumn 9, Issue 10, 2013, Pages

  Correia, Bruno ^a   Cerqueira, Sofia A ^b   Beauchemin, Chantal ^c   Pires de Miranda, Marta ^b   Li, Shijun ^c   Ponnusamy, Rajesh ^a   Rodrigues, Lénia ^b   Schneider, Thomas R ^d   Carrondo, Maria A ^a   Kaye, Kenneth M ^c   Simas, J Pedro ^b   McVey, Colin E ^a  

^a INSTITUTO DE TECNOLOGIA QUÍMICA E BIOLÓGICA   (Portugal)

^b UNIVERSITY OF LISBON   (Portugal)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BROMODOMAIN CONTAINING PROTEIN 4; LATENCY ASSOCIATED NUCLEAR ANTIGEN; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; CRYSTAL STRUCTURE; DNA BINDING; DNA SEQUENCE; FLOW CYTOMETRY; FLUOROMETRY; GEL MOBILITY SHIFT ASSAY; HERPES SIMPLEX VIRUS 2; IN SITU HYBRIDIZATION; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PERSISTENT VIRUS INFECTION; REAL TIME POLYMERASE CHAIN REACTION; SURFACE PLASMON RESONANCE; VIRUS DNA CELL DNA INTERACTION; VIRUS LATENCY; VIRUS RECOMBINANT; VIRUS REPLICATION; WESTERN BLOTTING; X RAY DIFFRACTION;

DNA, VIRAL; MUTATION; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN STRUCTURE, TERTIARY; RHADINOVIRUS; VIRAL PROTEINS; VIRUS LATENCY;

EID: 84887309755     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003673     Document Type: Article

References (63)

1. Simas JP, Efstathiou S, (1998) Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis. Trends Microbiol 6: 276-282.
2. Speck SH, Ganem D, (2010) Viral latency and its regulation: lessons from the gamma-herpesviruses. Cell Host Microbe 8: 100-115.
3. Nash AA, Dutia BM, Stewart JP, Davison AJ, (2001) Natural history of murine gamma-herpesvirus infection. Philos Trans R Soc Lond B Biol Sci 356: 569-579.
4. Cardin RD, Brooks JW, Sarawar SR, Doherty PC, (1996) Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells. J Exp Med 184: 863-871.
5. Sunil-Chandra NP, Efstathiou S, Nash AA, (1992) Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo. J Gen Virol 73 (Pt 12):: 3275-3279.
6. Flano E, Kim IJ, Woodland DL, Blackman MA, (2002) Gamma-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells. J Exp Med 196: 1363-1372.
7. Thorley-Lawson DA, (2001) Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1: 75-82.
8. Ballestas ME, Kaye KM, (2001) Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA. J Virol 75: 3250-3258.
9. Cotter MAII, Subramanian C, Robertson ES, (2001) The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen binds to specific sequences at the left end of the viral genome through its carboxy-terminus. Virology 291: 241-259.
10. Garber AC, Hu J, Renne R, (2002) Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication. J Biol Chem 277: 27401-27411.
11. Hu J, Garber AC, Renne R, (2002) The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J Virol 76: 11677-11687.
12. Komatsu T, Ballestas ME, Barbera AJ, Kelley-Clarke B, Kaye KM, (2004) KSHV LANA1 binds DNA as an oligomer and residues N-terminal to the oligomerization domain are essential for DNA binding, replication, and episome persistence. Virology 319: 225-236.
13. Lim C, Sohn H, Lee D, Gwack Y, Choe J, (2002) Functional dissection of latency-associated nuclear antigen 1 of Kaposi's sarcoma-associated herpesvirus involved in latent DNA replication and transcription of terminal repeats of the viral genome. J Virol 76: 10320-10331.
14. Schwam DR, Luciano RL, Mahajan SS, Wong L, Wilson AC, (2000) Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen mediates dimerization, transcriptional repression, and targeting to nuclear bodies. J Virol 74: 8532-8540.
15. Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC, et al. (2006) The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA. Science 311: 856-861.
16. Ballestas ME, Chatis PA, Kaye KM, (1999) Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284: 641-644.
17. Cotter MAII, Robertson ES, (1999) The latency-associated nuclear antigen tethers the Kaposi's sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells. Virology 264: 254-264.
18. Hung SC, Kang MS, Kieff E, (2001) Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc Natl Acad Sci U S A 98: 1865-1870.
19. Ilves I, Kivi S, Ustav M, (1999) Long-term episomal maintenance of bovine papillomavirus type 1 plasmids is determined by attachment to host chromosomes, which Is mediated by the viral E2 protein and its binding sites. J Virol 73: 4404-4412.
20. Lehman CW, Botchan MR, (1998) Segregation of viral plasmids depends on tethering to chromosomes and is regulated by phosphorylation. Proc Natl Acad Sci U S A 95: 4338-4343.
21. Yates JL, Warren N, Sugden B, (1985) Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313: 812-815.
22. Bastien N, McBride AA, (2000) Interaction of the papillomavirus E2 protein with mitotic chromosomes. Virology 270: 124-134.
23. Habison AC, Beauchemin C, Simas JP, Usherwood EJ, Kaye KM, (2012) Murine Gammaherpesvirus 68 LANA Acts on Terminal Repeat DNA To Mediate Episome Persistence. J Virol 86: 11863-11876.
24. Paden CR, Forrest JC, Tibbetts SA, Speck SH, (2012) Unbiased Mutagenesis of MHV68 LANA Reveals a DNA-Binding Domain Required for LANA Function In Vitro and In Vivo. PLoS Pathog 8: e1002906.
25. Marques S, Efstathiou S, Smith KG, Haury M, Simas JP, (2003) Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes. J Virol 77: 7308-7318.
26. Fowler P, Marques S, Simas JP, Efstathiou S, (2003) ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J Gen Virol 84: 3405-3416.
27. Moorman NJ, Willer DO, Speck SH, (2003) The gammaherpesvirus 68 latency-associated nuclear antigen homolog is critical for the establishment of splenic latency. J Virol 77: 10295-10303.
28. An FQ, Compitello N, Horwitz E, Sramkoski M, Knudsen ES, et al. (2005) The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest. J Biol Chem 280: 3862-3874.
29. Shamay M, Krithivas A, Zhang J, Hayward SD, (2006) Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA. Proc Natl Acad Sci U S A 103: 14554-14559.
30. Cai QL, Knight JS, Verma SC, Zald P, Robertson ES, (2006) EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog 2: e116.
31. Rodrigues L, Filipe J, Seldon MP, Fonseca L, Anrather J, et al. (2009) Termination of NF-kappaB activity through a gammaherpesvirus protein that assembles an EC5S ubiquitin-ligase. EMBO J 28: 1283-1295.
32. Li X, Liang D, Lin X, Robertson ES, Lan K, (2011) Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen reduces interleukin-8 expression in endothelial cells and impairs neutrophil chemotaxis by degrading nuclear p65. J Virol 85: 8606-8615.
33. Ottinger M, Christalla T, Nathan K, Brinkmann MM, Viejo-Borbolla A, et al. (2006) Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. J Virol 80: 10772-10786.
34. Ottinger M, Pliquet D, Christalla T, Frank R, Stewart JP, et al. (2009) The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. J Virol 83: 4423-4434.
35. Grundhoff A, Ganem D, (2003) The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids. J Virol 77: 2779-2783.
36. Bochkarev A, Barwell JA, Pfuetzner RA, Furey W Jr, Edwards AM, et al. (1995) Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein EBNA 1. Cell 83: 39-46.
37. Dell G, Wilkinson KW, Tranter R, Parish J, Leo Brady R, et al. (2003) Comparison of the structure and DNA-binding properties of the E2 proteins from an oncogenic and a non-oncogenic human papillomavirus. J Mol Biol 334: 979-991.
38. Reisman D, Yates J, Sugden B, (1985) A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol 5: 1822-1832.
39. Han SJ, Hu J, Pierce B, Weng Z, Renne R, (2010) Mutational analysis of the latency-associated nuclear antigen DNA-binding domain of Kaposi's sarcoma-associated herpesvirus reveals structural conservation among gammaherpesvirus origin-binding proteins. J Gen Virol 91: 2203-2215.
40. Kelley LA, Sternberg MJ, (2009) Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4: 363-371.
41. You J, Srinivasan V, Denis GV, Harrington WJ Jr, Ballestas ME, et al. (2006) Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes. J Virol 80: 8909-8919.
42. Kelley-Clarke B, De Leon-Vazquez E, Slain K, Barbera AJ, Kaye KM, (2009) Role of Kaposi's sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence. J Virol 83: 4326-4337.
43. Kelley-Clarke B, Ballestas ME, Srinivasan V, Barbera AJ, Komatsu T, et al. (2007) Determination of Kaposi's sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA binding. J Virol 81: 4348-4356.
44. Stebbins CE, Kaelin WG Jr, Pavletich NP, (1999) Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science 284: 455-461.
45. Stanley BJ, Ehrlich ES, Short L, Yu Y, Xiao Z, et al. (2008) Structural insight into the human immunodeficiency virus Vif SOCS box and its role in human E3 ubiquitin ligase assembly. J Virol 82: 8656-8663.
46. Lin A, Wang S, Nguyen T, Shire K, Frappier L, (2008) The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4. J Virol 82: 12009-12019.
47. Baxter MK, McPhillips MG, Ozato K, McBride AA, (2005) The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4. J Virol 79: 4806-4818.
48. Kabsch W, (2010) Xds. Acta Crystallogr D Biol Crystallogr 66: 125-132.
49. Evans P, (2006) Scaling and assessment of data quality. Acta Crystallogr D Biol Crystallogr 62: 72-82.
50. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, et al. (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658-674.
51. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213-221.
52. Emsley P, Cowtan K, (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126-2132.
53. Chen VB, Arendall WB, (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66: 12-21.
54. Krissinel E, Henrick K, (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372: 774-797.
55. Krieger E, Joo K, Lee J, Raman S, Thompson J, et al. (2009) Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8. Proteins 77 Suppl 9: 114-122.
56. Schrödinger, LLC (2010) The PyMOL Molecular Graphics System, Version 1.5.0.3.
57. McNicholas S, Potterton E, Wilson KS, Noble ME, (2011) Presenting your structures: the CCP4mg molecular-graphics software. Acta Crystallogr D Biol Crystallogr 67: 386-394.
58. De Leon Vazquez E, Kaye KM, (2011) The internal Kaposi's sarcoma-associated herpesvirus LANA regions exert a critical role on episome persistence. J Virol 85: 7622-7633.
59. Adler H, Messerle M, Wagner M, Koszinowski UH, (2000) Cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome. J Virol 74: 6964-6974.
60. Pires de Miranda M, Alenquer M, Marques S, Rodrigues L, Lopes F, et al. (2008) The Gammaherpesvirus m2 protein manipulates the Fyn/Vav pathway through a multidocking mechanism of assembly. PLoS One 3: e1654.
61. Simas JP, Bowden RJ, Paige V, Efstathiou S, (1998) Four tRNA-like sequences and a serpin homologue encoded by murine gammaherpesvirus 68 are dispensable for lytic replication in vitro and latency in vivo. J Gen Virol 79 (Pt 1):: 149-153.
62. Wu SY, Chiang CM, (2007) The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem 282: 13141-13145.
63. Belkina AC, Denis GV, (2012) BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer 12: 465-477.