InterPro domain: IPR036600

This entry represents the paired amphipathic helix (PAH) repeat. Sin3 proteins have at least three PAH domains (PAH1, PAH2, and PAH3) [ 1 , 2 ]. They are components of a co-repressor complex that silences transcription, playing important roles in the transition between proliferation and differentiation. Sin3 proteins are recruited to the DNA by various DNA-binding transcription factors such as the Mad family of repressors, Mnt/Rox, PLZF, MeCP2, p53, REST/NRSF, MNFbeta, Sp1, TGIF and Ume6 [ 3 ]. Sin3 acts as a scaffold protein that in turn recruits histone-binding proteins RbAp46/RbAp48 and histone deacetylases HDAC1/HDAC2, which deacetylate the core histones resulting in a repressed state of the chromatin [ 4 ]. The PAH domains are protein-protein interaction domains through which Sin3 fulfils its role as a scaffold. The PAH2 domain of Sin3 can interact with a wide range of unrelated and structurally diverse transcription factors that bind using different interaction motifs. For example, the Sin3 PAH2 domain can interact with the unrelated Mad and HBP1 factors using alternative interaction motifs that involve binding in opposite helical orientations [ 5 ].

Structurally, PAH2 is composed of four helices arranged in an open up-and-down bundle fold which binds alpha-helical peptides.

1. Solution structure of the mSin3A PAH2-Pf1 SID1 complex: a Mad1/Mxd1-like interaction disrupted by MRG15 in the Rpd3S/Sin3S complex. J. Mol. Biol. 408, 987-1000
2. Conserved themes in target recognition by the PAH1 and PAH2 domains of the Sin3 transcriptional corepressor. J. Mol. Biol. 375, 1444-56
3. The Mad1-Sin3B interaction involves a novel helical fold. Nat. Struct. Biol. 7, 1100-4
4. Extension of the binding motif of the Sin3 interacting domain of the Mad family proteins. Biochemistry 43, 46-54
5. HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. Nat. Struct. Mol. Biol. 11, 738-46