1OW1

Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.

Summary for 1OW1

• Entry DOI: 10.2210/pdb1ow1/pdb
• Descriptor: SMART/HDAC1 associated repressor protein (2 entities in total)
• Functional Keywords: beta-alpha-barrel, spoc domain, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q96T58
• Total number of polymer chains: 1
• Total formula weight: 21325.59

Authors

Schwabe, J.W.,Ariyoshi, M. (deposition date: 2003-03-28, release date: 2003-08-19, Last modification date: 2024-02-14)

Primary citation

Schwabe, J.W.,Ariyoshi, M.
A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling
Genes Dev., 17:1909-1920, 2003

PubMed Abstract: Spen proteins regulate the expression of key transcriptional effectors in diverse signaling pathways. They are large proteins characterized by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC domain. The specific biological role of the SPOC domain (Spen paralog and ortholog C-terminal domain), and hence, the common function of Spen proteins, has been unclear to date. The Spen protein, SHARP (SMRT/HDAC1-associated repressor protein), was identified as a component of transcriptional repression complexes in both nuclear receptor and Notch/RBP-Jkappa signaling pathways. We have determined the 1.8 A crystal structure of the SPOC domain from SHARP. This structure shows that essentially all of the conserved surface residues map to a positively charged patch. Structure-based mutational analysis indicates that this conserved region is responsible for the interaction between SHARP and the universal transcriptional corepressor SMRT/NCoR (silencing mediator for retinoid and thyroid receptors/nuclear receptor corepressor. We demonstrate that this interaction involves a highly conserved acidic motif at the C terminus of SMRT/NCoR. These findings suggest that the conserved function of the SPOC domain is to mediate interaction with SMRT/NCoR corepressors, and that Spen proteins play an essential role in the repression complex.

PubMed: 12897056
DOI: 10.1101/gad.266203

Experimental method

X-RAY DIFFRACTION (1.8 Å)