Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
DOI
PMC
 |
Open Access Gold |
|
as soon as is submitted to ZB.
The EBNA-2 N-terminal transactivation domain folds into a dimeric structure required for target gene activation.
PLoS Pathog. 11:e1004910 (2015)
Epstein-Barr virus (EBV) is a γ-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 β-strands and an α-helix which form a parallel dimer by interaction of two β-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 α-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.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
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
ISSN (print) / ISBN
1553-7366
e-ISSN
1553-7374
Journal
PLoS Pathogens
Quellenangaben
Volume: 11,
Issue: 5,
Article Number: e1004910
Publisher
Public Library of Science (PLoS)
Publishing Place
San Francisco
Non-patent literature
Publications
Reviewing status
Peer reviewed