TY - JOUR
T1 - Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery
AU - Oberoi, Jasmeen
AU - Fairall, Louise
AU - Watson, Peter J.
AU - Yang, Ji Chun
AU - Czimmerer, Zsolt
AU - Kampmann, Thorsten
AU - Goult, Benjamin T.
AU - Greenwood, Jacquie A.
AU - Gooch, John T.
AU - Kallenberger, Bettina C.
AU - Nagy, Laszlo
AU - Neuhaus, David
AU - Schwabe, John W.R.
N1 - Funding Information:
We thank P. Moody, P. Elliot and the beamline staff at DIAMOND and the European Synchrotron Radiation Facility for help with data collection. This work was supported by the Wellcome Trust (085408) and the UK Medical Research Council.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.1038/nsmb.1983
DO - 10.1038/nsmb.1983
M3 - Article
C2 - 21240272
AN - SCOPUS:79551626803
SN - 1545-9993
VL - 18
SP - 177
EP - 185
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 2
ER -