Structural and Functional Characterization of a Complex between the Acidic Transactivation Domain of EBNA2 and the Tfb1/p62 Subunit of TFIIH

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Infection with the Epstein-Barr virus (EBV) is linked to a number of human diseases and the nuclear antigen EBNA2 is one of nine viral latent proteins that plays a key role in EBV-linked diseases. EBNA2 activates expression of both viral and host gene in part through interaction between its C-terminal acidic transactivation domain (TAD) and a number of host transcriptional regulatory proteins including the general transcription factor IIH (TFIIH) and the histone acetyltransferase CBP/p300. In this manuscript, we demonstrate that the TAD of EBNA2 binds to the pleckstrin homology (PH) domain from the Tfb1/p62 subunit of TFIIH and determine a three-dimensional structure of a complex between EBNA2 and Tfb1/p62. The structure shows that three hydrophobic residues from the TAD of EBNA2 make key interactions at the complex interface and these same residues also play an important role in the binding to CBP/p300. Comparison of the structure of the EBNA2-Tfb1 complex with complexes containing acidic TADs from other proteins (p53 and VP16) bound to the same Tfb1/p62 target highlights the inherent versatility of these intrinsically disordered domains and how minor variations in positioning of key hydrophobic residues allows them to bind to common targets using different functional interfaces.

Vyšlo v časopise: Structural and Functional Characterization of a Complex between the Acidic Transactivation Domain of EBNA2 and the Tfb1/p62 Subunit of TFIIH. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004042
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004042

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