1ow1 | pdb_00001ow1
Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.
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| 1ow1, resolution 1.80Å | |||||||||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
Disease
Known disease associated with this structure: Megakaryoblastic leukemia, acute OMIM:[606077]
About this Structure
1OW1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling., Ariyoshi M, Schwabe JW, Genes Dev. 2003 Aug 1;17(15):1909-20. PMID:12897056
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