2N2J

Solution structure of the EBNA-2 N-terminal Dimerization (END) domain from the Epstein-barr virus

Summary for 2N2J

• Entry DOI: 10.2210/pdb2n2j/pdb
• NMR Information: BMRB: 19390
• Descriptor: Epstein-Barr nuclear antigen 2 (1 entity in total)
• Functional Keywords: homodimer, end domain, viral protein, ebna-2
• Biological source: Human herpesvirus 4 (HHV-4)
• Cellular location: Host nucleus matrix : P12978
• Total number of polymer chains: 2
• Total formula weight: 13326.90

Authors

Friberg, A.,Sattler, M. (deposition date: 2015-05-09, release date: 2015-06-10, Last modification date: 2024-05-15)

Primary citation

Friberg, A.,Thumann, S.,Hennig, J.,Zou, P.,Nossner, E.,Ling, P.D.,Sattler, M.,Kempkes, B.
The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.
Plos Pathog., 11:e1004910-e1004910, 2015

PubMed Abstract: 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.

PubMed: 26024477
DOI: 10.1371/journal.ppat.1004910

Experimental method

SOLUTION NMR