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

DOI: 10.1038/nsmb.1983 DOI Help
PMID: 21240272 PMID Help

Authors: Jasmeen Oberoi (MRC Laboratory of Molecular Biology) , Louise Fairall (University of Leicester) , Peter Watson (University of Leicester) , Ji-chun Yang (Medical Research Council) , Zsolt Czimmerer (University of Debrecen) , Thorsten Kampmann (University of Leicester) , Ben Goult (Univeristy of Leiecester) , Jacquie Greenwood (University of Leicester) , John Gooch (MRC Laboratory of Molecular Biology) , Bettina Kallenburger (MRC Laboratory of Molecular Biology) , Laszlo Nagy (University of Debrecen) , David Neuhaus (MRC Laboratory of Molecular Biology) , John Schwabe (University of Leicester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 18 (2) , PAGES 177 - 184

State: Published (Approved)
Published: January 2011
Diamond Proposal Number(s): 6388

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.

Journal Keywords: Amino; Animals; Cell; Crystallography; X-Ray; Humans; Intracellular; Mice; Models; Molecular; Nuclear; Biomolecular; Nuclear; Protein; Tertiary; Transducin

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 01/10/2011 21:22

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