title: The structure of Sif2p, a WD repeat protein functioning in the SET3 corepressor complex.
abstract: In Saccharomyces cerevisiae, the SIF2 gene product is an integral component of the Set3 complex (SET3C), an assembly of proteins with some homology to the human SMRT and N-CoR corepressor complexes. SET3C has histone deacetylase activity that is responsible for repressing a set of meiotic genes. We have determined the X-ray crystal structure of a 46 kDa C-terminal domain of a SET3C core protein, Sif2p to 1.55 A resolution and a crystallographic R-factor of 19.0%. This domain contains an unusual eight-bladed beta-propeller structure, which differs from other transcriptional corepressor structures such as yeast Tup1p and human groucho (Gro)/TLE1, which have only seven. We have demonstrated intact Sif2p is a tetramer and the N-terminal LisH (Lis-homology)-containing domain mediates tetramerization and interaction with another component of SET3C, Snt1p. Multiple sequence alignments indicate that a surface on the "top" of the protein is conserved among species, suggesting that it may play a common role in binding partner proteins. Since Sif2p appears to be the yeast homolog of human TBL1 and TBLR1, which function in the N-CoR/SMRT complexes, its structural and oligomeric properties are likely to be very similar.
authors.affiliation: Section of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cerna
authors.forename: David K
authors.initials: DK
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000235:genetics; D006655:Histone Deacetylases; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D004271:DNA, Fungal; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D012097:Repressor Proteins; C114411:SIF2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D006655:Histone Deacetylases