The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation
文献类型：期刊论文
| 作者 | Friberg, Anders1,2; Thumann, Sybille3; Hennig, Janosch1,2; Zou, Peijian1,2,4; Noessner, Elfriede5; Ling, Paul D.6; Sattler, Michael1,2,4; Kempkes, Bettina3 |
| 刊名 | PLOS PATHOGENS
 |
| 出版日期 | 2015-05-01 |
| 卷号 | 11期号:5 |
| 英文摘要 | Epstein-Barr virus (EBV) is a gamma-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2) is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END) domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four beta-strands and an a-helix which form a parallel dimer by interaction of two beta-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the alpha-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Microbiology ; Parasitology ; Virology |
| 研究领域[WOS] | Microbiology ; Parasitology ; Virology |
| 关键词[WOS] | EPSTEIN-BARR-VIRUS ; NUCLEAR-PROTEIN 2 ; LYMPHOCYTE GROWTH TRANSFORMATION ; NUCLEAR-PROTEIN-2 ACIDIC DOMAIN ; RBP-J-KAPPA ; BINDING-PROTEIN ; CELL-LINES ; IN-VITRO ; TRANSCRIPTION ; ANTIGEN-2 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000355269300049 |
| 源URL | [http://124.16.173.210/handle/834782/1483]  |
| 专题 | 天津工业生物技术研究所_蛋白质工程实验室 邹培建_期刊论文 |
| 作者单位 | 1.Helmholtz Zentrum Munchen, Inst Biol Struct, Natl Res Ctr Environm Hlth, Neuherberg, Germany 2.Tech Univ Munich, Ctr Integrated Prot Sci Munich, Chair Biomol NMR Spect, Dept Chem, Garching, Germany 3.Helmholtz Zentrum Munchen, Dept Gene Vectors, Natl Res Ctr Environm Hlth, Hematologikum, Neuherberg, Germany 4.Chinese Acad Sci, Ind Enzymes Natl Engn Lab, Tianjin Inst Ind Biotechnol, Tianjin, Peoples R China 5.Helmholtz Zentrum Munchen, Inst Mol Immunol, Natl Res Ctr Environm Hlth, Hematologikum, Neuherberg, Germany 6.Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA |
| 推荐引用方式 GB/T 7714 | Friberg, Anders,Thumann, Sybille,Hennig, Janosch,et al. The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation[J]. PLOS PATHOGENS,2015,11(5). |
| APA | Friberg, Anders.,Thumann, Sybille.,Hennig, Janosch.,Zou, Peijian.,Noessner, Elfriede.,...&Kempkes, Bettina.(2015).The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.PLOS PATHOGENS,11(5). |
| MLA | Friberg, Anders,et al."The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation".PLOS PATHOGENS 11.5(2015). |
入库方式： OAI收割
来源：天津工业生物技术研究所
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