Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery
Open Access
- 16 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 18 (2), 177-184
- https://doi.org/10.1038/nsmb.1983
Abstract
Assembly of transcriptional repression complexes involves the recruitment of different proteins to SMRT or its homolog NCoR. Now structural and functional work reveal the tetrameric organization of the oligomerization domain of TBL1 and map its interactions with SMRT and GPS2. The authors propose a model for the architecture and assembly of the corepressor complex. 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.Keywords
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