The structure of Sif2p, a WD repeat protein functioning in the SET3 corepressor complex

David Cerna, David K. Wilson

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 Å resolution and a crystallographic R-factor of 19.0%. This domain contains an unusual eight-bladed β-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.

Original languageEnglish (US)
Pages (from-to)923-935
Number of pages13
JournalJournal of Molecular Biology
Volume351
Issue number4
DOIs
StatePublished - Aug 26 2005

Fingerprint

Co-Repressor Proteins
R388
Yeasts
Proteins
Histone Deacetylases
Sequence Alignment
Genes
Saccharomyces cerevisiae
Carrier Proteins
X-Rays
WD40 Repeats

Keywords

  • Corepressor
  • Crystal structure
  • Protein-protein interaction
  • WD repeat

ASJC Scopus subject areas

  • Virology

Cite this

The structure of Sif2p, a WD repeat protein functioning in the SET3 corepressor complex. / Cerna, David; Wilson, David K.

In: Journal of Molecular Biology, Vol. 351, No. 4, 26.08.2005, p. 923-935.

Research output: Contribution to journalArticle

Cerna, David ; Wilson, David K. / The structure of Sif2p, a WD repeat protein functioning in the SET3 corepressor complex. In: Journal of Molecular Biology. 2005 ; Vol. 351, No. 4. pp. 923-935.
@article{3338817c03494a5492010d067e7459a2,
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 {\AA} resolution and a crystallographic R-factor of 19.0{\%}. This domain contains an unusual eight-bladed β-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.",
keywords = "Corepressor, Crystal structure, Protein-protein interaction, WD repeat",
author = "David Cerna and Wilson, {David K.}",
year = "2005",
month = "8",
day = "26",
doi = "10.1016/j.jmb.2005.06.025",
language = "English (US)",
volume = "351",
pages = "923--935",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - The structure of Sif2p, a WD repeat protein functioning in the SET3 corepressor complex

AU - Cerna, David

AU - Wilson, David K.

PY - 2005/8/26

Y1 - 2005/8/26

N2 - 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 Å resolution and a crystallographic R-factor of 19.0%. This domain contains an unusual eight-bladed β-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.

AB - 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 Å resolution and a crystallographic R-factor of 19.0%. This domain contains an unusual eight-bladed β-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.

KW - Corepressor

KW - Crystal structure

KW - Protein-protein interaction

KW - WD repeat

UR - http://www.scopus.com/inward/record.url?scp=23444444034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23444444034&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2005.06.025

DO - 10.1016/j.jmb.2005.06.025

M3 - Article

VL - 351

SP - 923

EP - 935

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -