2hi3
From Proteopedia
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Solution structure of the homeodomain-only protein HOP
Overview
Homeodomain-only protein (HOP) is an 8-kDa transcriptional corepressor, that is essential for the normal development of the mammalian heart., Previous studies have shown that HOP, which consists entirely of a, putative homeodomain, acts downstream of Nkx2.5 and associates with the, serum response factor (SRF), repressing transcription from SRF-responsive, genes. HOP is also able to recruit histone deacetylase (HDAC) activity, consistent with its ability to repress transcription. Unlike other classic, homeodomain proteins, HOP does not appear to interact with DNA, although, it has been unclear if this is because of an overall divergent structure, or because of specific amino acid differences between HOP and other, homeodomains. To work toward an understanding of HOP function, we have, determined the 3D structure of full-length HOP and used a range of, biochemical assays to define the parts of the protein that are, functionally important for its repression activity. We show that HOP forms, a classical homeodomain fold but that it cannot recognize double stranded, DNA, a result that emphasizes the importance of caution in predicting, protein function from sequence homology alone. We also demonstrate that, two distinct regions on the surface of HOP are required for its ability to, repress an SRF-driven reporter gene, and it is likely that these motifs, direct interactions between HOP and partner proteins such as SRF- and, HDAC-containing complexes. Our results demonstrate that the homeodomain, fold has been co-opted during evolution for functions other than, sequence-specific DNA binding and suggest that HOP functions as an adaptor, protein to mediate transcriptional repression.
About this Structure
2HI3 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Analysis of the structure and function of the transcriptional coregulator HOP., Kook H, Yung WW, Simpson RJ, Kee HJ, Shin S, Lowry JA, Loughlin FE, Yin Z, Epstein JA, Mackay JP, Biochemistry. 2006 Sep 5;45(35):10584-90. PMID:16939210
Page seeded by OCA on Wed Nov 21 11:46:57 2007
