Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

Jasmeen Oberoi, Louise Fairall, Peter J. Watson, Ji Chun Yang, Zsolt Czimmerer, Thorsten Kampmann, Benjamin T. Goult, Jacquie A. Greenwood, John T. Gooch, Bettina C. Kallenberger, Laszlo Nagy, David Neuhaus, John W.R. Schwabe

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84 Citations (Scopus)

Abstract

Eukaryotic transcriptional repressors function by recruiting large coregulatory complexes that target histone deacetylase enzymes to gene promoters and enhancers. Transcriptional repression complexes, assembled by the corepressor NCoR and its homolog SMRT, are crucial in many processes, including development and metabolic physiology. The core repression complex involves the recruitment of three proteins, HDAC3, GPS2 and TBL1, to a highly conserved repression domain within SMRT and NCoR. We have used structural and functional approaches to gain insight into the architecture and biological role of this complex. We report the crystal structure of the tetrameric oligomerization domain of TBL1, which interacts with both SMRT and GPS2, and the NMR structure of the interface complex between GPS2 and SMRT. These structures, together with computational docking, mutagenesis and functional assays, reveal the assembly mechanism and stoichiometry of the corepressor complex.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalNature Structural and Molecular Biology
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 1 2011

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Oberoi, J., Fairall, L., Watson, P. J., Yang, J. C., Czimmerer, Z., Kampmann, T., Goult, B. T., Greenwood, J. A., Gooch, J. T., Kallenberger, B. C., Nagy, L., Neuhaus, D., & Schwabe, J. W. R. (2011). Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery. Nature Structural and Molecular Biology, 18(2), 177-185. https://doi.org/10.1038/nsmb.1983