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

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)177-185
Number of pages9
JournalNature Structural and Molecular Biology
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

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Co-Repressor Proteins
Histone Deacetylases
Mutagenesis
Enzymes
Genes
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Oberoi, J., Fairall, L., Watson, P. J., Yang, J. C., Czimmerer, Z., Kampmann, T., ... 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

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery. / Oberoi, Jasmeen; Fairall, Louise; Watson, Peter J.; Yang, Ji Chun; Czimmerer, Zsolt; Kampmann, Thorsten; Goult, Benjamin T.; Greenwood, Jacquie A.; Gooch, John T.; Kallenberger, Bettina C.; Nagy, Laszlo; Neuhaus, David; Schwabe, John W.R.

In: Nature Structural and Molecular Biology, Vol. 18, No. 2, 01.02.2011, p. 177-185.

Research output: Contribution to journalArticle

Oberoi, J, Fairall, L, Watson, PJ, Yang, JC, Czimmerer, Z, Kampmann, T, Goult, BT, Greenwood, JA, Gooch, JT, Kallenberger, BC, Nagy, L, Neuhaus, D & Schwabe, JWR 2011, 'Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery', Nature Structural and Molecular Biology, vol. 18, no. 2, pp. 177-185. https://doi.org/10.1038/nsmb.1983
Oberoi, Jasmeen ; Fairall, Louise ; Watson, Peter J. ; Yang, Ji Chun ; Czimmerer, Zsolt ; Kampmann, Thorsten ; Goult, Benjamin T. ; Greenwood, Jacquie A. ; Gooch, John T. ; Kallenberger, Bettina C. ; Nagy, Laszlo ; Neuhaus, David ; Schwabe, John W.R. / Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery. In: Nature Structural and Molecular Biology. 2011 ; Vol. 18, No. 2. pp. 177-185.
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