1ow1
From Proteopedia
(New page: 200px<br /> <applet load="1ow1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ow1, resolution 1.80Å" /> '''Crystal structure o...) |
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caption="1ow1, resolution 1.80Å" /> | caption="1ow1, resolution 1.80Å" /> | ||
'''Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.'''<br /> | '''Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Spen proteins regulate the expression of key transcriptional effectors in | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1OW1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1OW1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OW1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ariyoshi, M.]] | [[Category: Ariyoshi, M.]] | ||
| - | [[Category: Schwabe, J | + | [[Category: Schwabe, J W.]] |
[[Category: beta-alpha-barrel]] | [[Category: beta-alpha-barrel]] | ||
[[Category: spoc domain]] | [[Category: spoc domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:22:14 2008'' |
Revision as of 12:22, 21 February 2008
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Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.
Contents |
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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