Analysis of the varicella-zoster virus IE62 N-terminal acidic transactivating domain and its interaction with the human mediator complex.

J Virol 2009 Jun 8;83(12):6300-5. Epub 2009 Apr 8.

Departments of Microbiology and Immunology, University at Buffalo SUNY, Buffalo, New York 14214, USA.

The varicella-zoster virus major transactivator, IE62, contains a potent N-terminal acidic transcriptional activation domain (TAD). Our experiments revealed that the minimal IE62 TAD encompasses amino acids (aa) 19 to 67. We showed that the minimal TAD interacts with the human Mediator complex. Site-specific mutations revealed residues throughout the minimal TAD that are important for both activation and Mediator interaction. The TAD interacts directly with aa 402 to 590 of the MED25 subunit, and site-specific TAD mutations abolished this interaction. Two-dimensional nuclear magnetic resonance spectroscopy revealed that the TAD is intrinsically unstructured. Our studies suggest that transactivation may involve the TAD adopting a defined structure upon binding MED25.

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http://dx.doi.org/10.1128/JVI.00054-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687382PMC
June 2009

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