Structure and VP16 binding of the Mediator Med25 activator interaction domain
- 6 March 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 18 (4), 404-409
- https://doi.org/10.1038/nsmb.1997
Abstract
Eukaryotic transcription is regulated by interactions between gene-specific activators and the coactivator complex Mediator. Here we report the NMR structure of the Mediator subunit Med25 (also called Arc92) activator interaction domain (ACID) and analyze the structural and functional interaction of ACID with the archetypical acidic transcription activator VP16. Unlike other known activator targets, ACID forms a seven-stranded β-barrel framed by three helices. The VP16 subdomains H1 and H2 bind to opposite faces of ACID and cooperate during promoter-dependent activated transcription in a in vitro system. The activator-binding ACID faces are functionally required and conserved among higher eukaryotes. Comparison with published activator structures reveals that the VP16 activation domain uses distinct interaction modes to adapt to unrelated target surfaces and folds that evolved for activator binding.Keywords
This publication has 71 references indexed in Scilit:
- Architecture of the RNA polymerase II–TFIIF complex revealed by cross-linking and mass spectrometryThe EMBO Journal, 2010
- Shifting Players and Paradigms in Cell-Specific TranscriptionMolecular Cell, 2009
- TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shiftsJournal of Biomolecular NMR, 2009
- NMR Structure of the Complex between the Tfb1 Subunit of TFIIH and the Activation Domain of VP16: Structural Similarities between VP16 and p53Journal of the American Chemical Society, 2008
- Structure–system correlation identifies a gene regulatory Mediator submoduleGenes & Development, 2008
- Transcription regulation and animal diversityNature, 2003
- The VP16 Activation Domain Interacts with Multiple Transcriptional Components as Determined by Protein-Protein Cross-linking in VivoJournal of Biological Chemistry, 2002
- AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMRJournal of Biomolecular NMR, 1996
- NMRPipe: A multidimensional spectral processing system based on UNIX pipesJournal of Biomolecular NMR, 1995
- GAL4-VP16 is an unusually potent transcriptional activatorNature, 1988