NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: Structural similarities between VP16 and p53

Langlois, Chantal, Mas, Caroline, Di Lello, Paola, Jenkins, Lisa M. Miller, Legault, Pascale and Omichinski, James G. (2008) NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: Structural similarities between VP16 and p53. Journal of The American Chemical Society, 130 32: 10596-10604. doi:10.1021/ja800975h


Author Langlois, Chantal
Mas, Caroline
Di Lello, Paola
Jenkins, Lisa M. Miller
Legault, Pascale
Omichinski, James G.
Title NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: Structural similarities between VP16 and p53
Journal name Journal of The American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
1943-2984
1520-5126
Publication date 2008-08-13
Sub-type Article (original research)
DOI 10.1021/ja800975h
Open Access Status Not yet assessed
Volume 130
Issue 32
Start page 10596
End page 10604
Total pages 9
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Abstract The Herpes Simplex Virion Protein 16 (VP16) activates transcription through a series of protein/ protein interactions involving its highly acidic transactivation domain (TAD). The acidic TAD of VP16 (VP16TAD) has been shown to interact with several partner proteins both in vitro and in vivo, and many of these VP16 partners also bind the acidic TAD of the mammalian tumor suppressor protein p53. For example, the TADs of VP16 and p53 (p53TAD) both interact directly with the p62/Tfb1 (human/yeast) subunit of TFIIH, and this interaction correlates with their ability to activate both the initiation and elongation phase of transcription. In this manuscript, we use NMR spectroscopy, isothermal titration calorimetery (ITC) and site-directed mutagenesis studies to characterize the interaction between the VP16TAD and Tfb1. We identify a region within the carboxyl-terminal subdomain of the VP16TAD (VP16C) that has sequence similarity with p53TAD2 and binds Tfb1 with nanomolar affinity. We determine an NMR structure of a Tfb1/ VP16C complex, which represents the first high-resolution structure of the VP16TAD in complex with a target protein. The structure demonstrates that like p53TAD2, VP16C forms a 9-residue α-helix in complex with Tfb1. Comparison of the VP16/Tfb1 and p53/Tfb1 structures clearly demonstrates how the viral activator VP16C and p53TAD2 shares numerous aspects of binding to Tfb1. Despite the similarities, important differences are observed between the p53TAD2/Tfb1 and VP16C/Tfb1 complexes, and these differences demonstrate how selected activators such as p53 depend on phosphorylation events to selectively regulate transcription.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 34 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 34 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 14 Mar 2011, 21:41:31 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging