Solution NMR studies of apo-mSin3A and -mSin3B reveal that the PAH1 and PAH2 domains are structurally independent.
The evolutionarily conserved mammalian Sin3 (mSin3) transcriptional corepressor interacts with a diverse array of transcription factors mainly through two PAH (paired amphipathic helix) domains located near the N terminus. Previous studies suggested the possibility of interdomain interactions involving the PAH domains. Here, we show that the domains are structurally independent and the properties of the individual domains, such as the conformational heterogeneity and the ability of mSin3A PAH2 to homodimerize, are preserved in constructs that span both PAH domains. Our results thus suggest that the N-terminal segments of the Sin3 proteins are broadly available for interactions with other proteins and that the PAH domains are organized into structurally independent modules. Our data also rule out any heterotypic association between the paralogous mSin3A and mSin3B proteins via interactions involving the mSin3A PAH2 domain.
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Yuan
Y
He
Ishwar
I
Radhakrishnan
D000818:Animals; D001059:Apoproteins / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008322:Mammals; D012097:Repressor Proteins / Q000737:chemistry*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D012996:Solutions; D014157:Transcription Factors / Q000737:chemistry*
D001059:Apoproteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C115812:Sin3b protein, mouse; D012996:Solutions; D014157:Transcription Factors; D056264:Sin3 Histone Deacetylase and Corepressor Complex