Structure and VP16 binding of the Mediator Med25 activator interaction domain

Erika Vojnic; André Mourão; Martin Seizl; Bernd Simon; Larissa Wenzeck; Laurent Larivière; Sonja Baumli; Karen Baumgart; Michael Meisterernst; Michael Sattler; Patrick Cramer

doi:10.1038/nsmb.1997

Structure and VP16 binding of the Mediator Med25 activator interaction domain

Erika Vojnic, André Mourão, Martin Seizl, Bernd Simon, Larissa Wenzeck, Laurent Larivière, Sonja Baumli, Karen Baumgart, Michael Meisterernst, Michael Sattler, Patrick Cramer

Research output: Contribution to journal › Article › peer-review

89 Scopus citations

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.

Original language	English
Pages (from-to)	404-410
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	4
DOIs	https://doi.org/10.1038/nsmb.1997
State	Published - Apr 2011
Externally published	Yes

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title = "Structure and VP16 binding of the Mediator Med25 activator interaction domain",

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.",

author = "Erika Vojnic and Andr{\'e} Mour{\~a}o and Martin Seizl and Bernd Simon and Larissa Wenzeck and Laurent Larivi{\`e}re and Sonja Baumli and Karen Baumgart and Michael Meisterernst and Michael Sattler and Patrick Cramer",

note = "Funding Information: Ingelheim Fonds and Elitenetzwerk Bayern. A.M. was supported by a Ph.D. fellowship (SFRH/BD/22323/2005) from the Portuguese Foundation for Science and Technology (FCT). M. Sattler acknowledges support by the Deutsche Forschungsgemeinschaft, the European Commission (3D Repertoire LSHG-CT-2005-512028) and the Bavarian NMR Center. P.C. was supported by the Deutsche Forschungsgemeinschaft, the Sonderforschungsbereich SFB646, the SFB Transregio 5, the Jung-Stiftung and the Fonds der chemischen Industrie. Funding Information: We thank D. Kostrewa and K. Leike for help, and T. Fr{\"o}hlich for help with MALDI and ESI experiments. M. Seizl was supported by the Boehringer",

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AU - Vojnic, Erika

AU - Mourão, André

AU - Seizl, Martin

AU - Simon, Bernd

AU - Wenzeck, Larissa

AU - Larivière, Laurent

AU - Baumli, Sonja

AU - Baumgart, Karen

AU - Meisterernst, Michael

AU - Sattler, Michael

AU - Cramer, Patrick

N1 - Funding Information: Ingelheim Fonds and Elitenetzwerk Bayern. A.M. was supported by a Ph.D. fellowship (SFRH/BD/22323/2005) from the Portuguese Foundation for Science and Technology (FCT). M. Sattler acknowledges support by the Deutsche Forschungsgemeinschaft, the European Commission (3D Repertoire LSHG-CT-2005-512028) and the Bavarian NMR Center. P.C. was supported by the Deutsche Forschungsgemeinschaft, the Sonderforschungsbereich SFB646, the SFB Transregio 5, the Jung-Stiftung and the Fonds der chemischen Industrie. Funding Information: We thank D. Kostrewa and K. Leike for help, and T. Fröhlich for help with MALDI and ESI experiments. M. Seizl was supported by the Boehringer

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Structure and VP16 binding of the Mediator Med25 activator interaction domain

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