The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation

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Epstein-Barr virus is an oncogenic γ-herpesvirus that may cause infectious mononucleosis in young adults and fatal lymphoproliferative disorders in immunocompromised patients and is associated with the pathogenesis of Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Epstein-Barr virus nuclear antigen 2 (EBNA-2) is a key regulator of viral and cellular gene expression which initiates and maintains a specific transcription program that promotes proliferation and differentiation of the infected B cell. EBNA-2 is a transcriptional activator that is recruited to DNA by cellular adaptor proteins, carries two transactivation domains, and has the capacity to form dimers or multimers. This study provides the first three-dimensional structure of the EBNA-2 N-terminal Dimerization (END) domain. Two END domain monomers, each consisting of four β-strands and a single α-helix, assemble into a dimer by interaction of two β-strands from each monomer in a parallel fashion. The dimer surface exposes residues that are critical for transactivation of target genes by EBNA-2. The dimeric fold of the EBNA-2 END domain has not been observed for any cellular protein and thus could provide a novel target for anti-viral therapeutics.

Vyšlo v časopise: The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004910
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004910

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